The Cannabis Plant Botanical

REFERENCES 23 Shoyama, Y., Fujita, T., Yamauchi, T., & Nishioka, I. (1968). Cannabi- Taura, F., Morimoto, S., & Shoyama, Y. (1995a). Cannabinerolic acid, a chromenic acid, a genuine substance of cannabichromene. Chemical cannabinoid from Cannabis sativa. Phytochemistry, 39, 457–458. and Pharmaceutical Bulletin, 16, 1157–1158. Taura, F., Morimoto, S., & Shoyama, Y. (1995b). First direct evidence Shoyama, Y., Hirano, H., & Nishioka, I. (1984). Biosynthesis of propyl for the mechanism of ∆1-tetrahydrocannabinolic acid biosynthesis. cannabinoid acid and its biosynthetic relationship with pentyl and Journal of the American Chemical Society, 117, 9766–9767. methyl cannabinoid acids. Phytochemistry, 23, 1909–1912. Taura, F., Morimoto, S., & Shoyama, Y. (1996). Purification and char- Shoyama, Y., Oku, R., Yamauchi, T., & Nishioka, I. (1972). Cannabis. acterization of cannabidiolic acid synthase from Cannabis sativa L. VI. Cannabicyclolic acid. Chemical and Pharmaceutical Bulletin, 20, Journal of Biological Chemistry, 271, 17411–17416. 1927–1930. Taura, F., Sirikantaramas, S., Shoyama, Y., Shoyama, Y., & Morimoto, Shoyama, Y., Tamada, T., Kurihara, K., Takeuchi, A., Taura, F., Arai, S., S. (2007a). Phytocannabinoids in Cannabis sativa: recent studies on Blaber, M., Shoyama, Y., Morimoto, S., & Kuroki, R. (2012). Struc- biosynthetic enzymes. Chemistry and Biodiversity, 4, 1649–1663. ture and function of ∆1-tetrahydrocannabinolic acid (THCA) syn- thase, the enzyme controlling the psychoactivity of Cannabis sativa. Taura, F., Sirikantaramas, S., Shoyama, Y., Yoshikai, K., Shoyama, Y., & Journal of Molecular Biology, 423, 96–105. Morimoto, S. (2007b). Cannabidiolic-acid synthase, the chemotype- determining enzyme in the fiber-type Cannabis sativa. FEBS Letters, Sirikantaramas, S., Morimoto, S., Shoyama, Y., Ishikawa, Y., Wada, Y., 581, 2929–2934. & Taura, F. (2004). The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of ∆1-tetrahydro- Taura, F., Tanaka, S., Taguchi, C., Fukamizu, T., Tanaka, H., Shoyama, cannabinolic acid synthase from Cannabis sativa L. Journal of Biologi- Y., & Morimoto, S. (2009). Characterization of olivetol synthase, a cal Chemistry, 279, 39767–39774. polyketide synthase putatively involved in cannabinoid biosyn- thetic pathway. FEBS Letters, 583, 2061–2066. Sirikantaramas, S. T. S., Morimoto, S., & Shoyama, Y. (2007). Recent advances in Cannabis sativa research: biosynthetic studies and its van Bakel, H., Stout, J., Cote, A., Tallon, C., Sharpe, A., Hughes, T., & potential in biotechnology. Current Pharmaceutical Biotechnology, 8, Page, J. (2011). The draft genome and transcriptome of Cannabis sa- 237–243. tiva. Genome Biology, 12, R102. Stout, J. M., Boubakir, Z., Ambrose, S. J., Purves, R. W., & Page, J. E. Yamamoto, H., Kimata, J., Senda, M., & Inoue, K. (1997). Dimethylallyl (2012). The hexanoyl-CoA precursor for cannabinoid biosynthesis is diphosphate: Kaempferol 8-dimethylallyl transferase in Epimedium formed by an acyl-activating enzyme in Cannabis sativa trichomes. diphyllum cell suspension cultures. Phytochemistry, 44, 23–28. The Plant Journal, 71, 353–365. Yamamoto, H., Senda, M., & Inoue, K. (2000). Flavanone 8-dimethylal- Suzuki, Y., Kurano, M., Esumi, Y., Yamaguchi, I., & Doi, Y. (2003). lyltransferase in Sophora flavescens cell suspension cultures. Phyto- Biosynthesis of 5-alkylresorcinol in rice: Incorporation of a puta- chemistry, 54, 649–655. tive fatty acid unit in the 5-alkylresorcinol carbon chain. Bioorganic Chemistry, 31, 437–452. Yang, X., Matsui, T., Kodama, T., Mori, T., Zhou, X., Taura, F., Noguchi, H., Abe, I., & Morita, H. (2016). Structural basis for olivetolic acid Taguchi, C., Taura, F., Tamada, T., Shoyama, Y., Tanaka, H., Kuroki, R., formation by a polyketide cyclase from Cannabis sativa. FEBS Jour- & Morimoto, S. (2008). Crystallization and preliminary X-ray dif- nal, 283, 1088–1106. fraction studies of polyketide synthase-1 (PKS-1) from Cannabis sativa. Acta Crystallographica. Section F, Structural biology and crystal- Zhao, P., Inoue, K., Kouno, I., & Yamamoto, H. (2003). Characterization lization communications, 64, 217–220. of leachianone G 2”-dimethylallyltransferase, a novel prenyl side- chain elongation enzyme for the formation of the lavandulyl group Taura, F., Dono, E., Sirikantaramas, S., Yoshimura, K., Shoyama, Y., & of sophoraflavanone G in Sophora flavescens Ait. cell suspension cul- Morimoto, S. (2007). Production of ∆1-tetrahydrocannabinolic acid tures. Plant Physiology, 133, 1306–1313. by the biosynthetic enzyme secreted from transgenic Pichia pastoris. Biochemical and Biophysical Research Communications, 361, 675–680. Zuurbier, K. W. M., Fung, S. -Y., Scheffer, J. J. C., & Verpoorte, R. (1998). In-vitro prenylation of aromatic intermediates in the biosynthesis of bitter acids in Humulus lupulus. Phytochemistry, 49, 2315–2322. I.  Setting the scene, botanical, general and international aspects

Index A Adaptive Poisson–Boltzmann Solver empirical support, e25, e26 (APBS), 686 theory, e24 AA. See Arachidonic acid (AA) leading to cannabis use in middle and high α-Amino-3-hydroxy-5-methyl-4- ADB. See Aggressive, disruptive behavior (ADB) school, e23 isoxazolepropionic acid empirical studies supporting, e24 (AMPA), 803 ADCA. See Alcohol and other Drugs theory, e23 receptor, 330 Council of Australia (ADCA) Agoraphobia, 65, 68 Abdominal viscera, sensory innervation, 440 Agouti-related protein (AgRP), 640 Ab initio protein folding, 684 Addiction, 715 Agricultural status, 8 Aboriginal and Torres Strait Islanders molecular mechanisms, 715 AgRP. See Agouti-related protein (AgRP) (ATSI), 105 Airway dynamics, 495 Abstinence, 489, 1097 Additive effects, 211, 212 AjA. See Ajulemic acid (AjA) Abstinence rates, e199 Adenylyl cyclase, 560 Ajulemic acid (AjA), 676 Abstinence violence effects (AVE), 1062 ADHD. See Attention-deficit/hyperactivity AKT1 gene, 64, 82 Abuse screening Alcohol, 80, 321 urine sample, use of, 988 disorder (ADHD) Alcohol and other Drugs Council of Australia chromatographic screening, 988 Adjunct therapy, 824 immunoassay, 988 Adolescent (ADCA), 1078 AC. See Amygdaloid complex (AC) Alcohol dependence, 1026 Academic performance antidrug media campaign targeting, 216 Alcohol-IAT, 270 chronic marijuana use, impact of, 290 cannabis use, 311 Alcohol-induced steatosis, e123 ACC. See Anterior cingulate cortex (ACC) levels of endocannabinoids and Alcohol, smoking and substance involvement Acetaminophen, 453 Acetylcholine (ACh), 830 cannabinoid receptors, 30 screening test (ASSIST), e171–e178 Acetyl-CoA, 15 as a phase of vulnerability for addiction, 143 psychometric performance, e178 carboxylase, 15 prevention and intervention program, 1037 Alcohol use disorders identification test Acetylhydrolase (AChE), 830 substance abuse, 1049 ACh. See Acetylcholine (ACh) vulnerability for THC effects in, 144 (AUDIT), e169 AChE. See Acetylhydrolase (AChE) Adult Memory and Information Processing Alcohol withdrawal, 873 Achievement goal Alkylindole compound, 984 cannabis use, relation with, 289 Battery Form A and B, 71 Alkylresorcinol moiety, 15 Acidic precursor, 708 Advanced cancer Allergic contact dermatitis, 545 ACP-CoA transacylase, 15 Allergic reaction, 518 Acquired immunodeficiency syndrome symptoms Allodynia, 906 (AIDS), 106, 199 anorexia/early satiety, 860 Allosteric agonism, 577 ACR. See American College of Rheumatology constipation, 860 Alpha-7 nicotinic receptors, 745 (ACR) dry mouth, 860 ALS pharmacology, e103 Action outcome associations dyspnea, 860 (A-O associations), 268 fatigue/lack of energy, 860 binge pattern, e105 Acute cannabis exposure, 380 nausea/vomiting, 860 and cannabis, e105 driving ability, 380 pain, 860 laboratory studies, 381 animal studies, e105–e107 attention, 381 Adverse drug reaction (ADRs) human studies, e107–e108 brain imaging, 386 associated with cannabinoids, 203 dopaminergic deficits, e105 decision making, 381 exchange-diffusion model, e104 motor inhibition and impulsivity, 381 Adverse health effects, increased risk, 30 hyperthermia, e105 time perception, 381 AEA. See Anandamide (AEA); See also mephedrone, e105 working memory, 381 METH-binging activate, e105 on-road studies, 387 N-Arachidonoylethanol-amine (AEA) methylone, e105 simulator studies, 386 AER. See Ascending enteric reflex (AER) neurotoxicity, e105 Acute postoperative pain, 451 2-AG. See 2-Arachidonoylglycerol (2-AG) serotoninergic deficits, e105 mechanism, 451 Age Alveolar macrophage number, 498 Acyl-activating enzyme (AAE), 15 Alzheimer disease (AD), 405, 734, 803, Acyl-CoA synthetase, 15 at first exposure to cannabis, 30 AD. See Alzheimer disease (AD); See also of first use is related to cannabis use 805, 963 Alzheimer’s dementia (AD) Alzheimer’s dementia (AD), 829 disorder risk, 35 American Academy of Neurology, 910 Aggressive, disruptive behavior (ADB), e19 American College of Rheumatology in elementary school leading to later (ACR), e159 cannabis use, e21 American court responses to shared use, 194 American Criminal Justice System, 189, 195 analyzed data collected from Dutch adolescents as part of TRAILS, e23 empirical support, e21, e22 theory, e21 using data from the Raising Health Children (RHC) study, e23 leading to ADB in middle and high school, e24 1115

1116 Index American drug court model, 194 regulation disorders, 299, 872 American soldier, drug abuse, e151 insulin-like growth factor-I, 866 cannabis, 304–305 Amidosulfone, 600 keratinocyte growth factor, 866 course of γ-Aminobutyric acid (GABA), 559, 806 cannabis use, effects of, 305 4-Aminopyridine (4-AP), 797 Anger, 182 dependence, 301 5-Aminosalicylic acid (5- ASA), 932 Angiogenesis, e118 incidence of CUD, risk of, 305 Amisulpride, 873, 887 Animal models, e132, 538, 705, 709 lifetime abuse, 301 Amitriptyline, e161 marijuana, effect of, 872 Amotivational syndrome, 66, e204, 289 of multiple sclerosis (MS) prevalence of past-year cannabis use, 301 AMP. See Amphetamine CBD, effect of, 899–900 three-year incidence AMPA. See α-Amino-3-hydroxy-5-methyl-4- experimental autoimmune lifetime cannabis user vs. nonuser, 302 encephalomyelitis (EAE) model, 899 isoxazolepropionic acid (AMPA) Theiler’s murine encephalomyelitis virus like behaviors, e137, 651 AMPA glutamate receptor, 734 (TMEV) induced model, 899 Anxiolytic effects, e134 AMPH. See Amphetamine 4-AP. See 4-Aminopyridine (4-AP) Amphetamine (AMPH), e102, e151, 181, of Parkinson’s and Alzheimer’s disease, 49 Apathy evaluation scale, 289 Animal studies, 507 321, 1008 ANS. See Autonomic nervous system (ANS) motivation score, 290 as Benzedrine, e103 Antagonists, 535 APBS. See Adaptive Poisson–Boltzmann biological properties, e103 chemical structures, e103 HcrtR1, 535 Solver (APBS) dopaminergic neuronal activity, e104 HcrtR2, 535 Aphrodisiac, 181 physiological concentrations, e104 Anterior cingulate cortex (ACC), e54 APINACA N-(4-hydroxypentyl), 985 treatment for, attention-deficit/ Anticholinergics, 47 Apoptosis, e114, e116, e119 Anticipatory nausea (AN), 704 hyperactivity disorder (ADHD), e103 Anticonvulsant effects, 434 cannabinoid, effect of MAPKs Amplified fragment length polymorphisms Anticonvulsant properties, 432 stimulation, 865 Antidepressants, 47 (AFLP), e7 Antidrug campaigns, e156 APP. See Amyloid precursor protein (APP) AMPs. See Antimicrobial peptides (AMPs) Not in My Corps, e156 Appetite, 643, 655 Amygdala, e54 Antidrug task forces, 124 Appetitive behavior, 269 Amygdala reactivity, 360 Antiepileptic drug (AED), 433, 435 Apprehended driver Amygdaloid complex (AC), e141 pharmacoresistant epilepsy, 433 Amyloid precursor protein (APP), 829 Antiexcitotoxic and antiinflammatory finding, 851 β-Amyloid protein, e137 synthetic cannabinoid variants, AN. See Anticipatory nausea (AN) properties, 49 Analgesia, 456, 823 Antimicrobial peptides (AMPs), 544 detection of, 852 Antinociception, 741 Arachidonate-based lipids anandamide cannabinoid, effect of, 961 Antiobesity agents, 654 Analysis of biological samples, 986–995 Antioxidant, 49 (AEA), 283 Antioxidant capacity, e125 Arachidonic acid (AA), 731 blood, 986–987 Arachidonoyl ethanolamine, 878 other matrixes, 991–995 by electron transfer, e125 N-Arachidonoylethanol-amine (AEA), 631 urine, 988–991 by hydrogen transfer, e127 2-Arachidonoylglycerol (2-AG), 81, 407, 452, Analysis of plant material, 985 Antiproliferative activity of cannabinoids Analysis of pure substance, 985 intracellular mechanisms underlying, e114 556, 607, 617, 641, 732, 878 Analytical challenge, 984–985 biosynthesis, 618 Analytical issue, 1010 actions beyond CB1/CB2 receptors, e116 effects, 617 immunoassay, related to, 1010 antitumoral action of cannabinoids in metabolism, 617 mass spectrometry (MS), related to, 1010 receptors, 621 other cannabinoid, related to, 1010 vitro, e114 targets, 621 THC, related to, 1010 mechanism of cannabinoids proapoptotic Arterial hypotension, 512 Analytical technique, 982–983 Arvanil, 924 Anandamide (AEA), 452, 512, 593, 617, 672, action–inhibition of prosurvival 5- ASA. See 5-Aminosalicylic acid (5- ASA) pathways, e114–e115 ASC. See Ascorbic acid (ASC) 789, 872, 878, 943 ceramide in cannabinoid Ascending enteric reflex (AER), 932 biosynthesis, 618 signaling, e115 Ascorbic acid (ASC), e127 effects, 617 contribution of ER-stress and ASSIST. See Alcohol, smoking and substance levels, 415 autophagy to cannabinoids-induced metabolism, 617 cell death, e117 involvement screening test (ASSIST) of network lipids, 620 inhibition of prosurvival pathways in Associative memory, 268 receptors, 621 antitumoral action of cannabinoids, AT. See Attention REM, effect on, 878 e116 Atherosclerosis, 490 sleep induction role of ER stress and autophagy in Atomoxetine, 1033, 1034 cannabinoid-induced cell death, Atopic dermatitis, 546 adenosine, molecule, activation of, 879 e115–e116 Atrial fibrillation, 489 role in, 879 Antipsychotic doses, 47 Attention, 71, 155, 157, 262 sleep modulation, effect on, 878 Antiretroviral therapy, 911 Attention-deficit/hyperactivity disorder SWS, effect on, 878 Anti-TNFα. See Antitumor necrosis factor targets, 621 alpha (anti-TNFα) (ADHD), e65, e103 Ancient Egypt Antitumor necrosis factor alpha associations between ADHD, ODD/CD, historical perspectives, for cannabis (anti-TNFα), 932 Antiviral immunity, 509 and cannabis use, e66 usage, 111 Anxiety, e132, 182, 824 and cannabis use comorbidity, e65 Androgen receptor activity cannabis, 311 causality, e66 childhood ADHD, e66 cross-sectional research, e65 externalizing disorders, e66

Index 1117 impact of THC AND CBD content, e67–e69 B consequences of cannabis use, 427 mediating factors, e67 dose–response relationship between retrospective studies, evidence for, e66 Baclofen, 773, 943, 1032, 1071 Attention deficits, cannabis users, e65 BACS symbol coding. See Brief assessment of cannabis use and age at onset, Attitude, 217, 218 425, 426 AUDIT. See Alcohol use disorders cognition in schizophrenia (BACS) genetic vulnerability models, 426 symbol coding environmental mediation of genetic identification test (AUDIT) BAD. See Bipolar affective disorder (BAD) influences, 426 Australia Barbiturates, 456 gene-environment interaction, 426 Basal ganglia disorder genetic confounding, 426 alcohol use increases during cannabis cannabis, use of, 917 hypomanic/manic episode, 424 abstinence, 103 Huntington disease, 917 neurobiology of cannabis in, 425 Parkinson disease, 917 cortical glutamate levels, role in, 425 among young adults, cannabis use, 102 Basal ganglia–thalamocortical circuit, 919 psychoactive compounds, 425 attitudes toward cannabis in 1994, 102 Basophil activation test (BAT), 524 pathophysiology and genetic risk, 424 cannabis cultivation, 102 principle, 524 prevalence of cannabis use and use cannabis law in, brief history of, 105 BAT. See Basophil activation test (BAT) disorders, in United States, 423 cannabis law reform in, 105 Bath salts, e153 psychotic disorders, and cannabis use, 423 cannabis use prevalence in states and Bayley Scales of Infant Development, 165–167 psychotic symptoms, 427 BBB. See Blood brain barrier (BBB) relationship between cannabis use territories, 103 B-cells, 518, 932 disorders and, 424 cigarette use increases during cannabis epitopes, 518 self-medication hypothesis, 424, 427 BD. See Bipolar disorder (BD) sociodemographic factors, 427 abstinence, 103 BDEOH. See Bond dissociation energy (BDEOH) symptoms and course of, 427 effects of cannabis use on Australian BDL rats. See Bile duct-ligated (BDL) rats types of, 422 BDNF. See Brain-derived neurotrophic factor Blood alcohol concentration (BAC), 239 communities, 107 (BDNF) Blood brain barrier (BBB), 432, 643 indigenous cannabis use, 105 BDS. See Botanical drug substance (BDS) Blood-retinal barrier (BRB), 763 Bed nucleus stria terminalis (BNST), e135 Blood screening method epidemiology, 105 Behavioral learning, 318 reversed phase LC coupled to mass medicinal cannabis in, 106 Behavioral methods, 249 spectrometry, use of, 986 cue-induced craving, 250 sample preparation cannabinoid replacement therapy reaction times, 249 liquid–liquid extraction, use of, 986 (CRT), 106 Behavioral tests, 742 BMI. See Body mass index (BMI) Behavior-specific responses, 456 BNST. See Bed nucleus stria terminalis (BNST) cannabis withdrawal symptoms, 107 Benton-visual-retention-test (BVRT), 888 Body mass index (BMI), 589, 933 mid-1990s, cannabis, illicit drug in, 102 Benzimidazoles, 600 after 3 months of cannabis treatment, 934 National Cannabis Policy (NCP), 106 Benzodiazepines, 47, 456 at study inception, 934 National Task Force on cannabis, 105 antagonist flumazenil, 775 Body packers, 123 patterns of cannabis usage in relation to chlordiazepoxide, 775 demographics of, 124 Benzoylindoles, 721 Body packing, 123 other substance misuse, 102 Betula verrucosa, 519 clinical perspective, 124 prevalence of CUD, 132 Bhageerath algorithm, 685 acute toxicity, 125 strategies for reducing misuse, 107 Bicyclic cores, 600 bowel obstruction, 125–126 benzimidazoles, 600 intestinal perforation, 126 cannabis public information bicyclic pyrazoles, 602 ethical considerations, 126–127 initiatives, 107 imidazopyridines, 602 legal considerations, 124 naphthyridines, 602 as means of smuggling, 123 types of cannabis products: availability, pyrazolopyridines, 602 security considerations, 127 price, and purity, 104 quinolones, 602 Body stuffing, 123 Bicyclic pyrazoles, 602 Boidae snake, e143 Australian Capital Territory (ACT), 105 Bile duct-ligated (BDL) rats, 512 Bond dissociation energy (BDEOH), e124 Australian Institute of Criminology Bioactive lipids, 617 Botanical drug substance (BDS), 960 Biological matrices, 238 Botany of Cannabis, 4 (AIC), 107 Biological receptors, 672 macroscopical features, 4 Australian Institute of Health and Welfare Biological stressor, 282 microscopical features, 5 Biological vulnerability factors, 62 BPD. See Bipolar disorder (BPD) (AIHW), 102, 105 Bipolar affective disorder (BAD), 788 Brain Authoritative style, 219 Bipolar disorder (BD), 209, 300 development, 152 age at onset, medication use, and suicide dopaminergic pathway, 280 characterized by, 219 attempts in, 425 Brain changes and cognitive functioning, Autonomic nervous system (ANS), 320 anecdotal reports, 424 in psychotic cannabis users over Auto-oxidation, 15 cannabis use disorders, 423 time, e60 Autophagy, e115, e117 and symptoms, 427 Brain-derived neurotrophic factor Autosome, e4 brain structure and functioning, 427 (BDNF), 717 Auxins, 10 cognition, 427 Brazilian research Protocol for Illegal Axial diffusivity (AD), 393 childhood trauma, 427 Drugs, e73 Axon clinical and epidemiological studies, 424 fiber connectivity, investigation of, 393 axonal integrity, measures of, 396 DW-MRI data, 393, 394 novel network-based statistic, 394 right fimbria of hippocampus and, 395 streamlines interconnecting right precuneus with, 396 white matter integrity perturbations, 394 white matter, whole-brain investigation of, 396 whole-brain tractography, 395 hippocampus, morphology in, 397 mechanisms of disturbance, 397 Azathioprine, 932

1118 Index BRB. See Blood-retinal barrier (BRB) antioxidant property, 895 vs. cannabis, 943–944 Breast cancer cells as antipsychotic drug, 789 vs. nicotine, 942–943 antipsychotic effects, 790 vs. opiates/opioids, 941 prolactin downregulation, 866 anxiolytic effects, e136 vs. stimulants, 941–942 Breast carcinoma, 865 arousal, effect on, 879 wakefulness, effect on, 879 Breastfeeding, 528 biotransformation, 899 Cannabidiolic acid (CBDA), e2, 7, 708 cannabinoid receptors, affinity with, 940 Cannabidiolic acid synthase (CBDAS), initiation and continuation, factors influencing, 528 CB1, 895, 940 e4, 15, 19 CB2, 895, 940 Cannabidivarin (CBDV), 21, 607 levels of neonatal exposure, 529 cellular targets, 901 Cannabidivarinic acid (CBDVA), 21 Brief assessment of cognition in derivatives, e124 Cannabigero, glaucoma treatment, use in, 880 δ opioid receptors, effect on Cannabigerol (CBG), 104, 672, 709, 751, 959 schizophrenia (BACS) symbol allosteric modulation, 899 coding, 1088 dream retrieval, effect on, 879 α2-adrenoceptor, effect on, 960 Brief strategic family therapy (BSFT), 1049 electronic properties, e126 anorexia-cachexia syndrome induced Broaden and Build theory of positive endocannabinoid signaling system, effect emotion, 313 weight loss, treatment of, 964 Bronchoalveolar lavage, 498 on, 895 anxiolytic effect, 964 BSFT. See Brief strategic family therapy (BSFT) excretion, 899 cancer cell line Bullous lung disease, 501 functional activity modulation of Buproprion, 941, 943, 1031 cell proliferation inhibition, 964 Burden of disease study methods, details amygdala-hippocampus complex, 940 cannabinoid type-1 (CB1R), effect on, 960 of, 90 cingulate cortex, 940 cannabinoid type-2 (CB1R), effect on, 960 case definition, 90 parahippocampal gyrus, 940 λ-carrageenan-evoked hypersensitivity, DisMod-MR modeling, 91 paralimbic regions, 940 systematic reviews, 90 temporo-limbic structure, 940 effect on, 961 Bush cannabis, 104 glial modulating effects, 920 COX inhibition, role in, 961 Buspirone, 943, 1032, 1071 glutamate-mediated neurotoxicity, effect G-protein-coupled-receptor, effect on, 960 human oral epitheloid carcinoma, C on, 895 hangover effect, 879 inhibition of, 964 CAGE-AID. See Cut down-annoyed-guilty- 5-HT1A serotonin receptor, interaction intra ocular pressure reduction, 965 eye opener-adapted to include keratinocyte proliferation, inhibition of, 965 drug (CAGE-AID) with, 898 medical use, 961–965 intraventricular administration, 880 Calcitonin gene-related peptide (CGRP), 780 inverse agonist of CB2 receptor, 898 analgesia, 961–962 Calcium channels, 567 lateral hypothalamus infusion, 880 cancer, 963–964 California verbal learning test-II, 295 mechanisms of action, 789, 796, 895–899, 940 inflammation, 961–962 neuroprotective effect, 898 inflammatory bowel disease (IBD), learning and memory performance, 295 nucleoside-transporter-1, binding with, 898 Callus culture, 10 µ opioid receptors, effect on 962–963 cAMP. See Cyclic adenosine monophosphate mood disorders, 964 allosteric modulation, 899 neuroinflammation in multiple (cAMP) orphan receptor GPR55, antagonism of, 899 Canada, past year cannabis use by age peroxisome proliferator-activated receptors sclerosis, 963 other, 964–965 group, 39 (PPARs), effect on, 899 mesenchymal stem cell stimulation, 965 Cancer pharmacokinetics, 899 metabolism, 959 pharmacology, 895–899 pharmacokinetic, 959–961 cannabinoid, treatment with, 963 potential beneficial effects in human, 901 pharmacology, 959–961 Cancer anorexia–cachexia syndrome, 863–864 property actions, 961 targets, 961 anabolic factor, effect of, 863 anticraving, 940 phospholipase-A2 (PLA2), effect on, 960 growth hormone, 863 antidepressant, 940 plasma and brain pharmacokinetic, 959 insulin growth factor, 863 anxiolytic, 940 prostate cancer cell, effect on, 964 thyroid hormone, 863 mood stabilizer, 940 rat feeding behavior, effect on, 964 sedative, 940 Staphylococcus aureus, activity against, 965 leptin regulation system, role of, 863 psychoactivity, lack of, 940 testosterone synthesis in rat, inhibition proinflammatory cytokines, role of, 863 regional cerebral blood flow (rCBF), effect skeletal muscle breakdown, 863 of, 965 Candida albicans, e73 on, 940 therapeutic application, 962 CANDIS treatment program. See Cannabis reuptake of endocannabinoid anandamide, transient receptor potential (TRP) channels, disorder (CANDIS) treatment inhibition of, 940 effect on, 960 program schizophrenia, use in, 959 uptake of dopamine, inhibition of, 960 Cannabaceae, e2, 3 side effects, 792 Cannabigerolic acid biosynthesis, 17 Cannabichromene (CBC), 104, 959 sleep, effect on, 879–880 Cannabigerolic acid synthase (CBGAS), 15 Cannabichromenic acid synthase (CBCAS), sleep-wake cycle, effect on, 879 Cannabigerovarinic acid (CBGVA), 21 15, 19 social anxiety disorder (SAD), effect on, 940 Cannabimimetic compound, 982 Cannabidiol (CBD), 25, 63, 65, 80, 104, e123, structure, e124 detection time, 982 e132, 418, 432, 607, 672, 706, 751, 788, total sleep time, effect on, 879 psychoactive effect, 982 796, 814, 829, 895, 940, 959, 1010 toxicity, 899 Cannabimimetics, 554 activity of fatty acid amide hydrolase transient potential vanilloid receptor type-1 Cannabinoid, 473, 536, 547, 554, 593, 718, 723, (FAAH), inhibition of, 940 adenosine signaling, enhancement, 898 (TPVR-1), interaction with, 898 749, 761, 771, 940 animal model, effect on, 880 uptake of dopamine, inhibition of, 941 allergic skin diseases treatment, therapeutic antianxiety properties, e132 antiepileptic effects, in animal models, 798 potential, 547

Index 1119 analgesics, as, 933 regulation, 577 enterochromaffin cells, effect on, 862 antitumor effect, 865–866 signaling, 577 for epilepsy, 436 biological activity, 718 allosteric modulators, 575 intoxication, 317 biosynthesis, e2 advantages, 575 neuroprotectant effect, 873 bone-forming cells, e78 binding of orthosteric ligands, 576 pathway, 18 bone physiology, impact on, e73 proposed, 579 pharmacodynamic, 860 bone-resorbing cells, e78 antagonism, 512 pharmacokinetic, 860 cannabis smoke-generating apparatus, antagonists, 646, 651, 667 potential therapeutic application, 953–955 associated ion channel modulation, 567 precursor biosynthesis, 15 smoke exposure, e74 calcium channels, 567 with propyl side chains, 21 Cannabis smoke, impact of, e77 potassium channels, 567 psychological effects, 865 cell mediated immunity, effect on, 933 in axonal growth, 397 serotonin receptors, effect on, 862 chronic neuropathic pain, effect on, 933 brain dispersion, 861 side effect, 913 effect on bone metabolism, e78 canonical signaling, 566 endocannabinoids, e72 CB1-D2 heterodimer, 579 dizziness, 913 endogenous, 593 constitutive signaling, 568 dry mouth, 913 host response evaluation, in cell function, 861 feelings of intoxication, 913 GαI protein coupling, 566 gastrointestinal effects, 913 cultures, e73 G protein coupling promiscuity, 568 hunger, 913 impact on immune cell activity, e78 internalization, 853 loss of balance, 913 inflammatory pain, effect on, 933 inverse agonists, 653 sedation, 913 intraocular pressure, 749 knockout mice, 920, 932 specific receptor, 878 lipopolysaccharide (LPS), e72 location, 918 substance LPS-evoked macrophage activation, mediated anandamide signaling, 872 extracted from cannabis, 880 mood regulation, role in, 871 synthetic compound, 880 inhibition, 933 neutral antagonist, 651 system, in psychiatric disorders, 62 main component orexin 1 receptor heterodimer, 580 tetrad, 693 receptors polymorphism, 283 ∆9-tetrahydocannabivarin, 948 cannabidiol (CBD), 878 regulation, 569 and their precursors, 14 tetrahydrocannabinol (THC), 878 arrestin recruitment and signaling, 570 therapeutic use mast cell, inhibition, 933 desensitization, 569 CINV, 862 molecular targets for, 753 internalization and degradation, 570 vagal stimulation, effect on, 862 CB1, 753 reward and habit development, role in, 269 and visceral pain, 441 CB2, 754 signaling, 682 gastrointestinal tract, 442 neurobiological mechanisms, 536 transductions, 560 in pathophysiological states, 474 stimulation of, 393 small/large intestine, 444 colorectal cancer, 476 structural characteristics, 556 stomach, 444 functional disorders of lower GI tract, 474 Cannabinoid receptor 2 (CB2), 415, 442, 498, genitourinary tract, 445 inflammatory bowel diseases, 475 endometrium, 446 pharmacology, 595 554, 565, 584, 840, 848, 932, 940 kidney and ureter, 445 in physiological states, 473 polymorphisms. See CB2 polymorphisms ovary, 445 receptors, e73, 556 signal transductions, 560 prostate, 446 cell physiology, 559 structural characteristics, 556 testes and scrotum, 446 discovery of, 556 Cannabinoid receptors, 632, 723, 740 urinary bladder and urethra, 445 endogenous ligands, 556 cannabinoid CB-1 receptor. See heart, 441 function, 559 liver, 444 location, 559 Cannabinoid receptor 1 (CB1) pancreas, 444 studies. See Histomorphometric study, in rats cannabinoid CB-2 receptor. See Cannabinoids on brain function, acute effects synthetic, 721 THC, 940 Cannabinoid receptor 2 (CB2) of, e44 Th1 cytokine production, effect on, 933 transmembrane receptor during cognitive tasks, e44 Th2 cytokine production, effect on, 933 therapeutic potential in ocular disorders, 761 G protein-coupled receptor, 848 acute administration of delta-9-THC/ use in cancer, 859 Cannabinoid replacement therapy (CRT), 106 CBD/placebo condition, e44 vascular inflammatory diseases, influence Cannabinoids, 3, 14, 182, 185, 672, 932 attentional salience processing, e47 on, e73 analgesic effect, 864 emotional faces processing task, e46 visceral sensory nerve, effect on, 933 anandamide, 697 neuroimaging studies of acute Cannabinoid based medicines (CBMs) antiemetic effect, 862 adverse effect, 890 antitumor mechanisms, 865, 866 administration of THC and CBDin biosynthesis of, 18 naïve cannabis users, e45 neuropsychological performance, effect cannabichromen, 948 response inhibition task, e46 on, 890 cannabidiol, 948 sensory processing task, e46 cannabidiolic acid, 948 genetic vulnerability to the acute effects of Cannabinoid hyperemesis syndrome cannabidivarin, 948 cannabis, e47 (CHS), 952 cannabigerol, 948 acute effects on dopamine release, e48 clinical symptom moderation response inhibition task (Go, No-Go Cannabinoid receptor 1 (CB1), 90, 269, 327, Task) and AKT1 polymorphism, e47 392, 415, 442, 462, 495, 554, 565, 575, biochemical pathway, 860, 861 verbal learning task, e47 609, 651, 667, 840, 848, 871, 932, 940 dopamine receptors, effect on, 862 during resting state, e44 effects on anxiety, 865 after acute administration of agonists, 565 emesis inhibition, 953 delta-9-THC or CBD, e44 allosteric ligands, 575 allosteric modulation dimerization, 579

1120 Index prevention. See Cannabis prevention prolonged use Cannabinol (CBN), 104, 719, 751, 814, 880 consumption duration, 47 molecular composition, 719 craving, 1031, 1058, 1059 memory loss, 860 optical activity, 719 psychomimetic effects, 358 psychoactive, 719 diary example, 1063 and psychosis, 66, 82. See also Cannabis, scale, 1064 Cannabis, 48, e102, 358, 373, 478, 488, 495, daily-use and psychosis correlation 660, 740, 771 family socioeconomic status, effect outcomes, 358 recreational use, 281, 840, 849 abstinence, 1030 of, 972 related disorders (CRD), 730 abuse, 943 dependence, 943, 1038, 1048, 1097 psychosocial treatment, CBT, use of, 1057 related neural substrate dependence, 41 face to face treatment linking associative effect, 269 acute effects on movement, 373 cognitive behavioral therapy related problems, 25, 30 addiction (CBT), 1049 resin usage, 478 contingency management, 1049 screening, 388 development and maintenance, motivational interviewing, 1049 biological matrices for, 388 1058–1059 self-initiated cessation family therapy, 1048 adolescent, 1037 compulsive use, 1059 brief strategic family therapy cultural values, role of, 1043 high risk situations (HRS), 1058, 1059 (BSFT), 1049 decision-making, role of, 1039 predisposing factor, 1058 functional family therapy (FFT), 1049 emerging adult, 1037 addicts, 67 MDFT, 1049 ethnic culture, role of, 1043 airway dynamics, acute effects, 495 multisystemic therapy (MST), 1049 family cohesion, role of, 1040 allergens, 520 future intervention allergy. See Cannabis allergy problem behavior, associated, 1048 antineoplastic mechanism, 860 treatment, 1030 cultural/attitudinal stream-derived in Arabic medicine, 111 intervention, 1043 arteritis, 483 evaluated medications, 1032 associated stroke, 490 dependent youth intrapersonal stream-derived association intervention, 1043, 1044 with lower respiratory infection, 500 multidimensional family therapy, 1049 with pneumothorax, treatment need, 1048 goal orientation, role of, 1040 detection and traffic, 238–239 parental bonding, role of, 1042 pneumomediastinum, and bullous dopamine system, effect on, 269 sibling influences, role of, 1042 lung disease, 501 effects of higher exposure of, 29 social support system, role of, 1041 based medicinal extract (CBME), 910 endocannabinoid signaling, 269 spousal interaction, role of, 1042 based medicine administration and executive functioning. See Cannabis on strategies, 1042, 1043 sleep in human protocols, effect on, 881 cannabinoid receptor, effect on, 269 executive functioning, effects of distraction, 1042 cannabis abuse screening test. See Cannabis extract, mental disorder, treatment, 878 stimulus removal, 1042 abuse screening test (CAST) functional imaging studies, 361 victimization, role of, 1040 cessation, 1037 herbal leaf, 478 self-medicating benefit, 1039 triadic theory of influence, 1038 higher exposure, effects of, 29 and sexual behavior. See Cannabis and cessation, preparation for, 1061 hybrid cultivars, 7 chemical compound hyperemesis syndrome. See Cannabis sexual behavior tetrahydrocannabinol (THC), 840 smoking, 823 chronic pain management, 840 hyperemesis syndrome (CHS) cigarette, 373 induced psychosis, 48, 337 lung contamination with, 1018 classification of, 5 synaptic effects of endogenous in clubbing drug users genetic aspects, studies examining, 337 rates of using, 174 ischemic stroke, 487 cannabinoid, effect on, 1057 on cognition, effects of, 71 learning function, effect on, 1057 for therapeutic purposes. See Cannabis for and cognition in psychosis long-term use, changes in movement, 374 methodological issues to take into and lung cancer, 498 therapeutic purposes (CTP) account, 46 lung, chronic effects on, 495 and tobacco (CTS), 495 and cognitive deterioration, 65–66 treatment. See Cannabis treatment cognitive effects, in nonpsychosis alveolar macrophage number, 498 trichomes classification, 6 individuals, 360 chronic respiratory symptoms, 495 triggers psychosis, 49 and cognitive functions, comprehensive human bronchial pathology, 498 use. See also Cannabis use (CU) reviews for, 73 lung function, 496 on cognitive functions, tolerance to lung pathology, 498 accidental problem, 1057 effects of, 72 thoracic high-resolution computed addiction, development of, 1057 consumption, 122 in adolescents, 74–75. See also Adolescent effect of intervention, 1088 tomography, 497 appetite stimulation, 933 lifetime progression, 1075 in Medieval Arab World, 111 behavioral consequence, 1037 progression memory, effect on, 1057 codependence to illicit substances, 1057 comparative data of main and mental disorders, 210 cognitive distortion, 1058 prevalence, 1075 negative reinforcing effect, 1038 energy metabolism, effect on, 933 side effect patient reason, for not using, 1063 impulse control problem, 1057 dependence, 940 patients with schizophrenia, 361 initiation of, 34 euphoria, 940 as a learned behavior, 1058–1059 mental health side effect, 940 cognitive performance, 361 learning model, 1058 neurofunctional alterations, 367 mental disorder, development of, 1057 positive affect, 1038 motivating factor potency, 25, 26, 28 and exposure to THC, 26 conformity, 1057 preparation hashish, 840 marijuana, 840

Index 1121 emotional regulation, 1057 related problems gateway drug, e103 enjoyment, 1057 screening instrument, e169, e170, genetic factors, e103 experimentation, 1057 e178, e181 Cannabis dependence and mental feeling high, 1057 getting rid of boredom, 1057 screening instruments, e170 disorders, 64 relaxation, 1057 self-administrable, e172 anxiety disorders, 65 social enhancement, 1057 psychological consequence, 1037 self-report panic, 65 regulation of appetite, 933 prevalence data, e188 posttraumatic stress disorder, 65 sexually risky behavior, 1057 Australian general population, e188 social phobia, 65 weight gain stimulation, 933 European general population, e188 bipolar disorder, 65 use disorder. See Cannabis use disorder global drug survey, e188 depression, 64–65 United States general population, e188 Cannabis disorder (CANDIS) treatment (CUD) youth, e188 use in adolescents, 74–75 validity, e188–e190 program, e194–e196 use on cognitive functions affecting points, e189 aims, e195 concordance with biological case report, e197 gender differences for effect of, 76 measurements, e189–e190 delivery by use, social norms, and legal status, 38 withdrawal symptom, 133, 1038, smoking, e169 type of clinician, e195 Cannabis abuse screening test (CAST), exclusion criteria, e195 1067–1068, 1070 inclusion criteria, e195 N-acetylcysteine, effect of, 943 e178–e179, 972–973 study phase agonist replacement therapy, 943 application, 972–973 I, e198 buccal spray, use of, 943 Italian experience, 974–975 II, e199 anxiety, 944 computing a score therapy sessions, e196, e197 clinical implication, 1070–1071 treatment modules, e195–e196 Italian validated version, use of, 973 cognitive-behavioral strategies (CBTs), pharmacological treatment, 1071 independent variable, 974 psychosocial treatment, 1070 questionnaire, 973 e195–e196 DSM-5, according to, 1067–1068 statistical analyses motivational enhancement therapy anger, 1067 decreased appetite or weight main evidence, 975–977 (MET), e195 Cannabis allergy, 520 problem solving training, e196 loss, 1068 Cannabis expiation notice (CEN), 105 depressed mood, 1068 clinical manifestations, 521 Cannabis for therapeutic purposes (CTP), insomnia, 1067 diagnosis, 522 irritability, 1067 natural history, 525 312–313 nervousness, 1067 prevalence, 520 analgesic effect, 312 other symptoms, 1068 routes of exposure, 520 antiemetic property, 312 physical symptom, 1068 sensitization, 520 appetite-stimulating, 312 restlessness, 1068 treatment, 525 cancer-related chemotherapy, 312 sleep difficulty, 1067 Cannabis, and psychosis correlation, 414 future research direction, 314 vivid unpleasant dream, 1068 causality, 416–418 multiple sclerosis, 312 effects of CBD, 944 causes of, 417 pain-related anxiety, 313 gabapentin, effect of, 943 CBD/THC ratio and the risk of, 418 Parkinson’s diseases, 312 insomnia, 944 chronic disorders, 419 Cannabis hyperemesis syndrome lithium, effect of, 943 component cause of, 416, 417 lofexidine, effect of, 943 dopaminergic transmission, 416 (CHS), 466 mirtazapine, effect of, 943 endocannabinoid signaling, 416 complications, 468 nefazodone, effect of, 943 environmental factors, 418 diagnosis, 468 physical symptom metaanalysis estimated in young adults, features, 467 fever, 1068 pathogenesis, 467 stomach pain, 1068 United Kingdom, 419 treatment, 468 sweating, 1068 exposure predicted severity of, 415 Cannabis indica, e2, 5, 873 tremor, 1068 general population studies, effect of, 414 Cannabis intoxication acute, physical variations in time course, 1068–1070 genes and environment interact, 418 demand characteristic, 1069–1070 genetic vulnerability, 417 effects of, 81 zolpidem, effect of, 943 psychotogenic effects of, 418 Cannabis on executive functioning, withdrawal symptoms, 1030 schizophrenia, risk of, 417 Cannabis, e132 Cannabis and sexual behavior, 182–185 effects of, 73 effects on brain, and impact on main studies addressing, 184 attention, 74 positive and negative effects, 184 planning and decision-making, 74 cognition, e54 proposed explanations, for positive effects verbal fluency, 74 genome, e4 verbal learning and memory, 74 of cannabis at low doses, 185 working memory, 74 heterozygous state (BT/BD), e5 Cannabis compound, other Cannabis picture presentations homozygous BT/BT genotype, e5 behavioral studies, 251 problematic use, e169, e170, e178–e180 β-caryophyllin, 880 classical conditioning, 251 prevalence estimation, general cannabigerol, 880 event-related potential research, 253 cannabinol, 880 fMRI research, 253 population, e169–e170 dronabinol, 880 problems, e169 nabilone, 880 orbitofrontal cortex (OFC), 254 psychosocial hazards, e169 sleep, effect on, 880 orbitofrontal cortex in BESA brain Cannabis consumers, e102 estimated number of people, e102 space, 254 spatial resolution, 251 temporal resolution, 250, 251

1122 Index important features of earlier CU as a risk factor for CUD, 144 Cannabis prevention treatment availability, 1026 natural history of cannabis consumption, treatment cost, 1026 negative association, 311 effect of, 1074–1076 barrier, implications of, 1028 poor school performance, 290 school-based program computer-based intervention, 1028 primary motive affective-focused program, 1076 self-guided intervention, 1028 best practice, 1078–1083 smartphone app, 1028 CTP, 310 Australian program, 1078 cognitive behavioral therapy, 1028 recreational, 310 characteristic, 1081–1082 family systems approach, 1028 problematic use motivation in early onset European program, 1078 motivational enhancement therapy, 1028 identification process, 1081 Cannabis use (CU), 138 CU, 146 North American program, 1078 above threshold as a risk factor for psychosis, e30 other intervention and evaluation interpersonal sensitivity, e204 risk of DSM-IV cannabis dependence by detail, 1082–1083 obsessive-compulsiveness, e204 characteristic, 1076–1077 paranoid ideation, e204 age at first CU, 140 individual component, 1077 phobic anxiety, e204 salutary effect, 309 booster session, 1077 psychoticism, e204 self-report, e185 program facilitator, 1077 somatization, e204 program intensity, 1077 absenteeism, 290 methods, e186–e187 timing of delivery, 1077 across age groups, 36 global drug survey (GDS), e187 interactive program, 1076 across the lifespan, trends in, 35 guidelines in Europe, e186–e187 intervention and evaluation detail, 1080 age at first CU and CUD onset and the surveys in Australia, e187 knowledge-focused, 1076 surveys in United States, e187 main characteristic, 1077 course of CUD, 148 youth surveys, e187 noninteractive program, 1076 by age group in US (percentage), 37 resistance skills training, 1076 among older adults, 39 young age at CU onset and its association skills-focused program, 1076 anxiogenic effect, 311 with CUD risk, 139 type, 1076 associative memory assessment, 269–270 selective or targeted, 1076 on brain structure and function, chronic Cannabis use disorder (CUD), 34, 131, e194, universal, 1076 e195, e198, e199, 299, 823, 940, 1026, effects of, e48 1030, 1057, 1087 Cannabis Problems Questionnaire for functional neuroimaging studies, e48 adolescents (CPQ-A-S), e179 adolescent-community reinforcement under cognitive tasks, e49 approach (A-CRA), 133 Cannabis-related knowledges resting state, e48 and attitudes in context of medical use of, genetic vulnerability to chronic age at onset, medication use, and suicide 203–204 attempts in BD patients with and cannabis use and views, 200 cannabis use without, 425 drug prevention program at school, 203 and its effect on brain structure, e49 gender differences, and risk perception structural effects, e48 anecdotal reports, 424 among Polish students, 205 challenges associated, impact approach, 1059 relationship between self-reported brain structure and functioning, 427 cannabis use prevalence and risk minimization, e206–e208 clinical features, 132–134, 1060 perception bond in therapy, e208 clinical studies, 425 among European students, 200 concern/risk and cognition, 427 risk and protection factors influencing, 203 cognitive behavioral therapy, use of sources of information on illicit drugs target issues, e207–e208 reported by European young goals of therapy, e207–e208 case example, 1062–1064 people, 202 internet/computerized treatment, successful outcome, 1063–1064 substance use prevention programs, 201 therapeutic alliance, 1062 e206–e207 unsuccessful outcome, 1062–1063 Cannabis ruderalis, e2, 5 specialized cannabis clinics, e208 Cannabis sativa, 3, e72, 432, 441, 452, 554, 593, depressive outcome comorbid disorder adjusted odds ratios (AORs), 303 pharmacotherapy, 1033–1034 607, 849, 860, 873, 877, 932 confidence intervals (CIs), 303 publication distribution, 878 early comorbidities, challenge of, 428, 1059 sleep, effect on, 879 in CUD risk in the context of existing diagnosis, 1059 sleep latency, decrease in, 879 disorder, treatment of, 76 sleep-wake cycle, effect on, 879 models of, 145 dopamine and glutamate, 425 Cannabis sativa hexanoyl-CoA synthetase 1 as a risk factor for CUD, 143 dose–response relationship, age at onset in escalation of, 143 (CsHCS1 or CsAAE1), 15 euphoric effect, 309 bipolar disorder, 426 Cannabis sativa hexanoyl-CoA synthetase 2 higher rates of suspension, 290 dysphoria and negative psychological high-risk age periods for, 139 (CsHCS2 or CsAAE3), 15 implicit association test, 269–270 experiences, link between, 424 Cannabis sativa subsp. indica var. indica later environmental mediation, genetic childhood adversity, association (domesticated), 5 influences, 426 Cannabis sativa subsp. indica var. kafiristanica with, 292 evaluation, 1059 novelty-seeking behavior, association factor models, 427 (wild), 5 gender differences in severity markers, 133 Cannabis treatment, 1026, 1094 with, 292 genetic vulnerability models, 426 parents with prior criminality, high-risk age periods for incidence, 139 barrier, 1026–1028 integrative model of role of younger age at low perceived need, 1026 association with, 292 negative views from community, 1026 socially disadvantaged background, CU onset in CUD risk, 146–148 male to female ratio of lifetime cannabis association with, 292 lower school satisfaction, 290 use, 132 mesolimbic dopaminergic pathways, 425 modular treatment CANDIS program, e193 scientific evaluation, e198–e199

Index 1123 neurobiological mechanisms, 425 DW-MRI data, 393, 394 Catalepsy, 330, 651, 730 pharmacotherapy, 1032–1033 novel network-based statistic, 394 Catalepsy-like immobilization, 327 right fimbria of hippocampus and, 395 antidepressants and anxiolytic, use streamlines interconnecting right THC-induced, 327 of, 1032 involvement of precuneus with, 396 CB1 receptor, 327 cannabinoid agonist, use of, 1032 white matter integrity perturbations, 394 glutamatergic neuronal system, 330 glutamatergic agents, use of, 1033 white matter, whole-brain investigation nucleus accumbens, 328 other medication, use of, 1033 serotonergic neuronal system, 329 prevalence of cannabis use, 131 of, 396 prodromal phase, 424 whole-brain tractography, 395 Catechol-O-methyltransferase (COMT), 336 psychiatric disorder chronic inhibitor, 943 anxiety disorder, 1033 psychosocial stress bipolar disorder, 1033 Cathinone, e103 depression, 1033 dopamine response, to, 281 chemical structures of, e104 quality of life, daily functioning, and, 428 evidence for dysconnectivity, 393 relationship between BD and, 423, 424 CB1. See Cannabinoid receptor 1 (CB1) schizophrenia, 424 adult and adolescent, white matter CB2. See Cannabinoid receptor 2 (CB2) self-medication hypothesis, 424 microstructural alterations in, 393 CBC. See Cannabichromene (CBC) stage CB2 cannabinoid receptor gene (CNR2), 586 cognitive behavioral approach, 1061–1062 corpus callosum, 393 CBD. See Cannabidiol (CBD) DW-MRI studies, 393 CBDA. See Cannabidiolic acid (CBDA) sobriety, maintainance, 1061 white matter abnormalities, 393 CBDA synthase, e3 symptoms and course of BD, 427 evidence, 397 CBDA-synthase gene, e6 technology-assisted intervention, 1094 foot-in-the-door, e208 future directions, 397 DNA sequencing electropherogram of a computer-based intervention, 1094 non-face-to-face (non-F2F) treatment, e206 portion, e6 high technology based, 1094 schizophrenia, development of, 392 interactive voice response treatment engagement, e202 CBD/THC ratio, e4, e5 importance, e203 CBDV. See Cannabidivarin (CBDV) intervention, 1094 influence by, e204–e205 CBG. See Cannabigerol (CBG) low technology based, 1094 CB-GABA interactions, 773 mobile-based interventions, 1094 cannabis use, e204 CBG-free-CBG-BDS, 960 telemedicine, 1094 motivation, e204 CB1-knockout mice, e137 telephone counseling, 1094 physiological effects of cannabis, e204 CBM. See Cognitive behavioral model (CBM) transition from cannabis first use to, 132 risk perceptions, e205 CBME. See Cannabis, based medicinal extract treatment therapeutic alliance, e205 CBT method, 1060–1061 potential threats, e206 (CBME) premature treatment dropout, e205 CBMs. See Cannabinoid based medicines cognitive restructuring, 1060–1061 Cannabis withdrawal syndrome cognitive-behavioral approach, 1059 abstinence-induced sleep disruption, 1032 (CBMs) effectiveness, 135 pharmacotherapy, 1031–1032 CBN. See Cannabinol (CBN) services, 134–136 antidepressant, use of, 1031 CB2 polymorphisms, 586 in youth, effective treatment, 1048–1049 cannabinoid agonist, use of, 1031 Cannabis use disorders identification test evaluated medication, 1031 and bipolar disorder, 589 mood stabilizer, use of, 1031 and bone disorders, 588 (CUDIT), e170, e179–e180 other medication, use of, 1032 and cardiovascular disorders, 587 Cannabis use intervention sedative hypnotic, use of, 1032 and CNS disorders, 588 Canonical signaling, 566 and eating disorders, 589 computer-based, 1096 CapOpus trial, 1087 and immune system disorders, 586 computer-based counselor-guided, 1095 result, 1089 and liver disorders, 587 high-tech delivery, 1095 Capsaicin, 924 and schizophrenia, 589 Capsazepine, 924 CB2 Q63 polymorphism, 588 limitation, 1095 Carbon tetrachloride-induced hepatic and alcoholism, 588 lost to follow-up, 1095 and depression, 589 participant anonymity breach, risk damage, 509 CBT. See Cognitive behavioral therapy (CBT) of, 1095 autoimmune hepatitis, 509 CCD. See Cross-reactive carbohydrate liver fibrosis, effect of cannabinoids, 510 vs. low-tech delivery, 1098 Carboxyhemoglobin, 490 determinants (CCD) low-tech delivery, 1097–1098 Carboxylation, 15 CCl4-induced cirrhosis, 512 9-Carboxy-THC, 529 CD. See Celiac disease (CD); See also Crohn’s limitation, 1098 Cardiac embolism, 489 participant dropout, 1098 Cardiomyopathy, 482 disease (CD) participant self-report, risk of bias CART. See Cocaine, and amphetamine- CD activity index (CDAI), 933 in, 1098 CDAI. See CD activity index (CDAI) short follow-up assessment regulated transcript (CART) cDNA. See Complementary DNA (cDNA) period, 1098 β-Caryophylline, 878 cDNA/EST library, 15 CEDS. See Clinical endocannabinoid telecounseling intervention, 1097 antiinflammatory effect, 880 technology-assisted Case-control studies, 585 deficiency syndromes (CEDS) Caspases, e114 Celiac disease (CD), 587 age, effect of, 1098 CAST. See Cannabis abuse screening Cellular pathways comparison of, 1098 gender, effect of, 1098 test (CAST) cannabinoid, effect of, 865 Cannabis use problems identification test CAT. See Catalase (CAT) neurotransmitters release inhibition, 865 Catalase (CAT), 782 (CUPIT), e180–e181 Central nervous system (CNS), e105, e159, Cannabis users, 1026 534, 584, 593, 714, 796 axonal fiber connectivity, investigation Central neuropathic pain, by multiple of, 393 sclerosis, 909–911

1124 Index Cognitive functions, 47, 48, 50, e54, e55, e59, e60, 71, 262 Central sensitization, 906 Ciliary muscle, 756 Ceramide, e114, e115, e119 CINV. See Chemotherapy-induced nausea in cannabis users, 48 in current IQ, verbal memory, working in cannabinoid signaling, e115 and vomiting (CINV) Cerebellar motor impairment, 408 Cirrhotic mesenteric arteries, 512 memory span, and planning Cerebellum, 71 Cirrhotic rats, 512 ability, 49 Cerebral vasculitis, 490 Cisplatin-induced delayed emesis, 953 key facts of, 70 Cerebral vasoconstriction, 490 Citalopram, 329 psychotic patients, using cannabis, 48. Cerebrospinal fluid (CSF), 64, 283, 789 Client satisfaction questionnaire See also Explicative hypothesis Cerebrovascular effects, 483 related with cannabis use CF. See Cognitive functions (CSQ), 1088 risk factors and treatment of CFC models. See Contextual fear Climate schools model (CSM) program, impairments in, 76 in schizophrenia, 49 conditioning (CFC) models 1078, 1082 Cognitive impairments, 45 CGRP. See Calcitonin gene-related peptide Clinical Antipsychotic Trials of Intervention Cognitive independence model, 1060 Cognitive inhibitory control, 293 (CGRP) Effectiveness (CATIE) project, 48 Cognitive performance, 45, 47 Chalcone synthase (CHS), 15 Clinical endocannabinoid deficiency THC, effect of, 874 CHC. See Chronic hepatitis C (CHC) Cognitive restructuring method Chemical phenotype, e3 syndromes (CEDS), e162 behavioral, 1061 Chemokines, 544 Clinical test of impairment (CTI), 851 cognitive, 1060–1061 Chemopreventive agents, 818 Clinical trials, 453 emotional, 1061 Chemoreceptor trigger zone (CTZ), 862 Colonic transit Chemotaxonomic classification, 7 acute postoperative pain treatment with ∆9-tetrahydrocannabinol, effect of, 950 Chemotherapy-induced nausea and vomiting cannabinoids, 453 Colorectal cancer (CRC), 476 Communication, 219 (CINV), 860, 862–863, 953 Clubbing community, reasons for cannabis Comorbid, 47, 48, 75 neurotransmitters, role of, 862 use in, 176 attention deficit hyperactivity disorder marijuana, effect of, 874 dopamine, 862 gateway theory, 176–177 drug usage, 47 histamine, 862 short-term effects, 176 major depression, 1026 muscarine, 862 Clubbing culture, 171 Companionship, 310 serotonin, 862 Clubbing drugs, 172, 176 Comparative risk assessment (CRA), 91 pathogenesis, 862 Club drugs, e12, e15 Compatible trial, regions of activity within Chibouque, 111, 119 CM. See Contingency management (CM) group, 274 Childhood trauma Cannabinoids, 585 Complementary DNA (cDNA), 556 age at onset, substance abuse CNR2. See CB2 cannabinoid receptor gene Component resolved diagnosis (CRD), 524 and childhood trauma abuse dose Composite International Diagnostic (CNR2) Interview (CIDI), 47 effect, 212 CNR1, CNR2, and FAAH genes, 64 COMT. See Catechol-O-methyltransferase history link between cannabis use CNR1 polymorphisms, 62 (COMT) CNS. See Central nervous system (CNS) COMT gene, 64, 66, 337, 418 and severe mental disorders, 211 Cocaine, 48, 162, 172, 181, 182, 321, 373, 1008 and cannabis use interactions, and the interaction between childhood sexual effect on risk for psychosis, e32 and amphetamine-regulated transcript evidences from case-only and case- abuse, cannabis abuse, and, 212 (CART), 780 control studies, e33 and mental disorders, 209 evidences from experimental and prone to illicit drug use, 210 dependence, 281 experience sampling method based questionnaire (CTQ), 211 marijuana, effect of, 874 studies, e37 substance abuse and childhood trauma evidences from longitudinal studies, e32 smuggling, 123 evidences from neuroimaging abuse dose effect, 211 Cognition, 48, 122, 361 studies, e37 Chinese hamster ovary K1 (CHO K1) cell cannabis use interaction, studies on, e37 in psychosis, 46 environmental factors interaction, e38 line, 566 Cognitive areas, studied in psychosis related genetic interactions and other biological CHIP assay. See Chromatin mechanisms, e38 to cannabis use, 46 methodological concerns and challenges, immunoprecipitation (CHIP) assay Cognitive assessment, 47 e38–e39 Chloroplast DNA (cpDNA), e8 Cognitive behavioral model (CBM), 1058 pleiotropic biological and behavioral Chlorpromazine (CPZ), 730, 862 Cognitive behavioral therapy (CBT), 135, effects of COMT gene, e37 CHO K1 cell line. See Chinese hamster ovary and effect of Val158Met polymorphism on e194–e196, e203, 1057, 1087, COMT activity, e32 K1 (CHO K1) cell line 1094, 1103 molecular variability and the risk for Cholinergic systems, 741 coping with cravings and urges, e196 psychosis, e30 Chromatin immunoprecipitation (CHIP) marijuana use treatment, 1103 COMT inhibitor. See Catechol-O-methyl principle, 1060 transferase (COMT) inhibitor assay, 724 psychoeducation, e195 Chronic cannabis, 490 refusal/social competence training, e196 relapse prevention (RP), e196, 1057 abuse, 463 sobriety state, effect on, 1057 effects, 81 target day preparation, e196 understanding consumption patterns, e196 Chronic hepatitis C (CHC), 587 Cognitive deficits, 44 Chronic obstructive pulmonary disease Cognitive disorder, 874 marijuana, effect of, 874 (COPD), 496 Cognitive domains, 225 Chronic pain model, 451 Cognitive effects, 823 cannabis use in healthy subjects, 45 mechanism, 451 long-term use of cannabis in psychotic Chronic pelvic pain syndrome, 446 patients, 45 Chronic prostatitis, 446 nicotine, 47 CHS. See Cannabinoid hyperemesis syndrome (CHS)

Index 1125 COMT Val158Met polymorphism, 337 Crohn’s disease (CD), 475, 932 Cyclooxygenase (COX), 796 Conceptual model of achievement enhanced endocannabinoid, 954 inhibition assay, 960 gastrointestinal (GI) tract, effect on, 932 inhibitor indomethacin, 512 effects on substance use during marijuana smoking, effect of, 954 adolescence, 291 Cyclooxygenase-2 (COX-2), 724, 803 Cross-reactivity, 518 pathway, 731 Conditioned gaping, 705 carbohydrate determinants (CCD), 520 acute nausea, 705 syndrome, 521 Cyclopropanoylindoles, 721 anticipatory nausea, 705 CYP. See Cytochromes P450 (CYP450) Cross-sectional data CYP1A1 inhibitors, 814 Conditioned place preference (CPP), 666 limitation, 302 CYP1A2 inhibitors, 814 Condition interaction significance, 302 CYP1 enzymes significant regions of activity, 275 Cross-sectional studies, 46 active-site cavity, 817 Conduct disorder (CD), e23, e66 CRT. See Cannabinoid replacement inhibition, 816 Confounding effect, 224 Confounding factor, 311 therapy (CRT) significance, 818 Cryptotis parva, 953 Cysteinyl leukotrienes, 512 cannabis use assessment, 311 Crystallization, 687 Cytochromes P450 (CYP450), 621, 814 polydrug use, 311 CSA. See Controlled Substances Act (CSA) sample selection, 311 CSF. See Cerebrospinal fluid (CSF) enzymes, e123 Confounding variables, 48 CSM program. See Climate schools model Cytokinins, 10 Conservation initiatives, 8 Constitutive signaling, 568 (CSM) program D Consultant-participant alliance, 1087 CSQ. See Client satisfaction questionnaire Contact allergic inflammation, 545 DAGL. See Diacylglycerol lipase (DAGL) proinflammatory chemokines, (CSQ) d-amphetamine, 941 CTP. See Cannabis for therapeutic purposes D1 and D2 receptors, 64 secretion of, 545 DAST-10. See Drug abuse screening test-10 Content of successful drug prevention (CTP) CTQ. See Childhood trauma, questionnaire (DAST-10) program at school, 203 DAST-28. See Drug abuse, screening test Contextual fear conditioning (CFC) (CTQ) CTS. See Cannabis, and tobacco (CTS) (DAST-28) models, e135 CTT. See Critical tracking task (CTT) DAT. See Divided attention task (DAT) Contingency management (CM), e194 CTZ. See Chemoreceptor trigger zone (CTZ) DBSNP. See Single nucleotide polymorphism Continuous performance test (CPT), e55, 1088 CU. See Cannabis use (CU) Contrave, clinical trial, 650 CUD. See Cannabis use disorder (CUD) database (DBSNP) Controlled drug CUDIT. See Cannabis use disorders DC. See Dendritic cell (DC) Decision-making (DM), 71 identity determination identification test (CUDIT) Deep layers of the superior colliculus chemical structure Cue-elicited craving, 320 infrared spectroscopy (IR), 982 Cue-reactivity (dlSC), e141 mass spectrometry (MS), 982 Degree of tolerance, 456 nuclear magnetic resonance cannabis study, 322–323 ∆Eiso. See Stabilization energy (∆Eiso) spectroscopy (NMR), 982 paradigm, 321 Delinquency, 216, 219 virtual reality experiment, 323 Delta-9-Tetrahydrocannabinol, effect of Controlled Substances Act (CSA), e155 Cultivation techniques, of Cannabis, 9 COPD. See Chronic obstructive pulmonary indoor cultivation, 9 vs. cannabidiol, 875 outdoor cultivation, 9 Delusions, 44 disease (COPD) in vitro micropropagation, 9 Dementia, 829, 874 Cortisol-awakening response, 280 Cultural/attitudinal predictor COX. See Cyclooxygenase (COX) attitudes, 1041 marijuana, effect of, 874 COX-2. See Cyclooxygenase-2 (COX-2) cognitive processing, 1040–1041 Demographics Cox regression, 499 emerging adulthood (EA), 1040–1041 C3-phytocannabinoids, 21 larger social environment, 1040 characteristics, 54 C5-phytocannabinoids, 21 pro-drug use myth, 1041 of drug trade, 123 CPP. See Conditioned place preference (CPP) CUPIT. See Cannabis use problems Dendritic cell (DC), 518 C-prenylation of divarinic acid (DA), 21 Dendritic spines, 734 CPZ. See Chlorpromazine (CPZ) identification test (CUPIT) Density Functional Theory (DFT) CRAFFT, e179 Current Cannabis varieties, 7 Cranial mesencephalon, e145 Current drug dependence diagnosis, 47 methodology, e124 Craving Current scientific classification, of Cannabis, 7 Department of Health and Human Services Cut down-annoyed-guilty-eye opener-adapted cannabis, 317 (DHHS), e187 cue-reactivity, 320–321 to include drug (CAGE-AID), e169 Depolarization-induced suppression of environment stimuli, 319 CVS. See Cyclic vomiting syndrome (CVS) memory encoding disruption, 322 Cyclic adenosine monophosphate inhibition (DSI), 632 reason for relapse, 317 Depression, 182 theoretical etiology, 318–319 (cAMP), 593 theoretical issue, 321–322 accumulation, 579 cannabis, 311 CRC. See Colorectal cancer (CRC) cannabis dependence, 311 CRD. See Cannabis, related disorders (CRD) assays, 586 Depressive symptoms, 415 Criminal justice system, 216 dependent protein kinase A, 566 Descriptive epidemiology of aggressive/ CRIP1a, 683 inhibition, 822 3D structure prediction, 683 Cyclic vomiting syndrome (CVS), 467 disruptive behavior, e20 CRIP1a-CB1R model, 685 Cycloalkylcarboxamide group, 600 Descriptive epidemiology of cannabis Critical tracking task (CTT), 380 Cyclobenzaprine, e161 Cyclohexylphenol (CP) synthetic use, e20 Designer drugs, e151, 841 cannabinoid, 841 Detection of drivers under the influence of cannabis (DUIC), 387 Developmental periods, risk factors for cannabis use during, e21 Deviant social milestones, 58

1126 Index Drug discrimination, 771 interoceptive effects, 772 DFT methodology. See Density Functional neurons, e30 neuropharmacological interactions, 772 Theory (DFT) methodology pathway, 319 Drug-free children, best practices for DHHS. See Department of Health and ventral tegmental area (VTA), 319 raising, 220 Human Services (DHHS) producing neurons, 918 release amphetamine-induced, 281 Drug interactions, 47, 437 Diabetes mellitus (DM), 780 reward-sensitive stimuli, 320 Drug readministration, 667 Diabetic dyslipidemia, 780 synthesis capacity, 290 Drug recognition expert (DRE) Diabetic neuropathy, 912 uptake blocker and releaser, 941 Diacylglycerol lipase (DAGL), 283, 618 ventral striatum level, 321 protocol, 849 Dopamine cells, 741 Drug-related activities, 124 inhibition, 624 Dopaminergic agonists, 788 Drug-relevant stimuli, 320 Diagnostic and Statistical Manual of Mental Dopaminergic hyperactivity, 824 Drug replacement, 57 Dopaminergic mesocorticolimbic Drugs and sexual behavior, 181 Disorders (DSM), e170, 299, 1067 Diaphoresis, 467 system, 534 type of, 182 Diazepam, 775 Dopaminergic system, 714 Drug-seeking behavior, 318 Dibenzopyran-numbering system, 14 DOPE scoring, 685 Diffeomorphic registration algorithm Dorsal motor nucleus of the vagus effect of CBD, 941 Drugs, for pregnant and nonpregnant (DARTEL), e55 (DMV), 948 Differential association theory, 189, 190 Dorsal portions of periaqueductal gray women, 168 Diffusion tensor imaging (DTI), 347, 393 Drug substitution, 54, 58, 59 (DPAG), e135 Drug testing, e152 in adolescent cannabis use, 348 Dorsal raphe nucleus (DRN), 705 Drug use disorders, cannabidiol, treatment in early phase psychosis, 347 Dorsolateral striatum (putamen), 269 Diffusion-weighted imaging (DWI), 491 Dorsomedial striatum (caudate), 269 with, 940 Digital necrosis, 483 Dose–response cannabis effects, 30, 49, 415 Drug use disorders identification test Digit-symbol-substitution task, 773 Dose–response relationships, 47 Dihydrocodeine, 912 Dose–response theory, 312 (DUDIT), e170 2, 5-Dimethoxy-4-iodoamphetamine DPAG. See Dorsal portions of periaqueductal Drug use in general population, 172–174 DRUID. See Driving-under-the-influence-of- (DOI), 329 gray (DPAG) 2, 4-Dinitro-1-fluorobenzene (DNFB), 545 DPPH. See 1, 1-diphenyl-2-picryhydrazyl drugs (DRUID) Diphenhydramine, 912 DSI. See Depolarization-induced suppression 1, 1-Diphenyl-2-picryhydrazyl (DPPH), e127 (DPPH) Disability-adjusted life years (DALYs), 95–98 Dravet syndrome, 434–436 of inhibition (DSI) Disability assessment schedule, 1088 DSM-5. See Diagnostic and Statistical Manual Disability weights, 91 clinical trial on cannabidiol, 436 Driving ability, 380 of Mental Disorders (DSM)-5 calculation of YLDs, YLLs and DALYs, 91 ∆9-Tetrahydrocannabinol (∆9-THC), 3, 62, 71, comorbidity adjustments, 91 attention, 380 comparative risk assessment (CRA), 91 critical tracking, 380 80, 373, 433, 440, 462, 467, 472, 660, data on regular (weekly or more frequent) decision-making, 380 704, 714, 723, 740, 782, 789, 796, 803, reaction time, 380 814, 829, 940 cannabis use in the past year, 92 Driving under influence of cannabis cannabidiol effects on brain stimulation DISC1 gene. See Disrupted-in- blood/serum concentrations of synthetic reward, 660 chemical structure of, 720 schizophrenia-1 (DISC1) gene cannabinoids, 850 in dyslipidemia, 782 Disrupted-in-schizophrenia-1 (DISC1) epidemiology of, 235 effect on CPP, 666 fatal crash studies, 237–238 in food intake and energy homeostasis, 783 gene, 346 hospital studies, 237 functional analogs, 719 Divalproex, 943, 1031 roadside surveys, 235–237 immunosuppressive effects, 783 Divided attention task (DAT), 380 Driving-under-the-influence-of-drugs metabolic route, 463 dlSC. See Deep layers of the superior metabolites excretion in urine, 784 (DRUID), 849, 1003 narcotic properties, 720 colliculus (dlSC) DRN. See Dorsal raphe nucleus (DRN) in oxidative stress, 782 DM. See Decision-making (DM) Dronabinol, 528, 912, 943, 953, 1071 physical dependence, 667 DMV. See Dorsal motor nucleus of the role in reward and dependence, 661 awoke less often, effect on, 880 in secretion of insulin, 782 vagus (DMV) sleep-wake cycle, effect on, 880 self-administration, 665 DNA banding, e3 synthetic CB1 receptor agonist, 880 self-administration in experimental DNA methylation, 726 Drug abuse, e151 animals, 665 DNA microarray, 726 craving, function of, 318 three-dimensional shape, 719 DNFB. See 2, 4-Dinitro-1-fluorobenzene dependence development, 281 ∆9-THC. See ∆9-Tetrahydrocannabinol in females, 182 (∆9-THC) (DNFB) screening test (DAST-28), 973 DTI. See Diffusion tensor imaging (DTI) Doctor–patient relationship, 531 side effects of, 181 Dual pathology, 67 DOI. See 2, 5-Dimethoxy-4-iodoamphetamine Drug abuse screening test-10 DUDIT. See Drug use disorders identification test (DUDIT) (DOI) (DAST-10), e181 DUIC. See Detection of drivers under the Domeperidone, 862 Drug addicts, 182 influence of cannabis (DUIC) Doose syndrome, 799 Duloxetine, e161 Dopamine (DA), 181, 254, 279, 425, 535, 714 THC analysis, chromatogram, 1023 Duration, frequency, and amount of Drug control and treatment of addiction cannabis usage, 73 craving development, 322 DWI. See Diffusion-weighted imaging (DWI) D2/D3 receptor, 321 fund (DCTAF), 119 examination, 290 Drug courts, 195 mesolimbic release, 319 Drug dependence, 873 mesolimbic reward system, 293 Drug detection kits, 999 mesolimbic system, 289, 321 neuronal firing, 416

Index 1127 Dyskinesia, 824, 833 Eicosanoids, 617 in bipolar disorder, 63 cannabinoid induced, 922 Electroencephalographic (EEG) activity, composition l-dopa-induced, 922 effect of cannabinoids, 923 433, 611 biochemical apparatus, 878 human study, 922 Electronic dance music (EDM), e15 endogenous agonist, 878 nonhuman primates study, 922 Elevated T-maze (ETM), e132 receptor, 878 Eligible Studies in depression, 62 Dysthymia, 1033 implicated in the pathogenesis of cases-control, key characteristics, e84 E Cohort, key characteristics of, e83 depression, 63 pooled approach/re-analysis of secondary link between stress, continuous cannabis EA. See Emerging adulthood (EA) EAE. See Experimental autoimmune data, e81 use, and psychosis, 282–283 ELISA. See Enzyme-linked immunosorbent in psychosis, 64 encephalopathy (EAE) schematic representation, 610 Early onset cannabis use, 73 assays (ELISA) sensory innervation, 440 EAS. See Encephalic aversion system (EAS) EMA. See Ecological momentary assessment sleep modulation, role in, 878 ECA. See Epidemiological catchment sleep, relation with, 878–879 (EMA); See also European Medicines Endocannabinoid system (ECS), 641, 651 area (ECA) Agency (EMA) Endogenous acetylcholine, 746 eCBs. See Endocannabinoids (eCBs) EMCDDA. See European Monitoring Centre Endogenous cannabinoid system (ECS), 71, Ecological momentary assessment for Drugs and Drug Addiction (EMCDDA) e162, 472, 544, 948. See also Microglia (EMA), 1103 Emerging adulthood (EA), 1040 2-arachidonoylglycerol, e162 Ecological momentary intervention characteristic cannabinoid agonists, direct effect on endless possibilities, belief on, 1040 (EMI), 1103 feeling in-between, 1040 receptors, 405–407 mobile technology, 1108 lifestyle, 1040 abnormal-cannabidiol receptors usage own identity establishment, 1040 self-focused, 1040 (abn-CBD), 406 addictive behavior change, 1103 EMI. See Ecological momentary intervention neurodegenerative diseases, treatment alcohol dependence, 1103 (EMI) mental health disorders, 1103 Emotional regulation, 62 in, 405 self-monitoring, 1103 Emperical article peroxisome proliferator-activated smoking cessation, 1103 summary of finding, 1042 ECS. See Endogenous cannabinoid system EMT. See Endocannabinoid membrane receptor (PPAR), 406 transporters (EMT) potential sites, sensitive to cannabinoid (ECS) Encephalic aversion system (EAS), e141 Ecstasy, e102, 162, 172, 373 Endocannabinoid, e72, e136, e141, e162, 753 compounds, 406 EDDRA. See Exchange on drug demand 2-arachidonoylglycerol (2-AG), e141 synthetic cannabinoid analogs, 406 arachidonylethanolamide, 753 transient receptor potential cation reduction action (EDDRA) 2-arachidonylglycerol, 753 EDM. See Electronic dance music (EDM) N-arachidonoyl ethanolamide, e141 channel (TRP), 406 EDTA. See Ethylenediaminetetraacetic acid O-arachidonoylethanolamine, e141 cannabinoid receptors, e162 other receptor, binding with CB1 receptors, 948 (EDTA) vanilloid-1 receptor (TRPV1), 878 CB2 receptors, 948 Education, 48 palmitoylethanolamide, 753 downstream effector of ECS EEG activity. See Electroencephalographic in pre- and postsynaptic neurons, e31 receptor deregulation, 408–410 (EEG) activity CB1, 878 downregulation and desensitization EETs. See Epoxyeicosatrienoic acid (EETs) CB2, 878 Effect sizes, 47 Endocannabinoid-hydrolysis inhibitors, 607 of, 408 Egypt Endocannabinoid membrane transporters effect of THC exposure in the neuronal (EMT), 473 cannabis abuse in selected population Endocannabinoid metabolism, 621 circuit, 408 groups, 115 Endocannabinoids anandamide, 327 experimental data on impact of Endocannabinoid signaling system (ECS), cannabis use in 282–283, 416 subchronic exposure to THC and patients with drug overdose, 115 component, 284 withdrawal, 410 patients with other medical HPA function, mediation of, 283 experimental data supporting, 409 conditions, 116 psychosis risk, 283–284 microglial reactivity in cerebellum, 408 psychiatric patients, 116 stress regulation, role in, 283–284 gut innervation controlling motility, role school and university students, 115 stress-responsive neural circuit, 282 in, 948 Endocannabinoids ligands anandamide, e162 cannabis, source of, 113 N-arachidonoylethanolamine, 617 localization of components in cigarette smoking and cannabis, 118 Endocannabinoids (eCBs) system, 63, 64, 81, gut, 472 current status of cannabis use in, 113 392, 405, 416, 452, 512, 609, 631, 651, in neurodegenerative diseases, 405 gender and demographic differences in 672, 741, 789, 860, 982 nonclassical receptor, 948 anandamide, 840 peroxisome proliferator-activated cannabis abuse, 116 in anxiety, 63 receptor, 948 hashish during 18th–20th Centuries, 111 2-arachidonoylglycerol, 840 transient receptor potential vanilloid-1 initiation of drug/cannabis abuse, 117 (TRPV1) channel, 948 Endometriosis, 446 drug abuse pattern among different eNOS protein expressions, 513 categories, 119 ENS. See Enteric nervous system (ENS) Entacapone, 943 Upper Egypt, 117 Enteric nervous system (ENS), 472 prevalence of factors associated with, and Enzyme inhibitors, 754 Enzyme-linked immunosorbent assays affecting, cannabis abuse, 114 (ELISA), 988 relevance of cannabis use to educational level and marital status in Lower Egypt, 118 social and economic factors, 118

1128 Index Enzymes involved in cannabinoid European School Survey Project on Alcohol F biosynthesis, 16 and Other Drugs (ESPAD), e178, e187, 199 FA. See Fractional anisotropy (FA) Epidemiological catchment area (ECA), 299 FAAH. See Fatty acid amide hydrolase Epidemiological studies, 415 Exchange-diffusion model, e104 Exchange on drug demand reduction action (FAAH) cannabis and psychosis, 82 FAAH-related activities, 445 migration and psychosis, 83 (EDDRA), 1078 Face-to-face (F2F) treatment, e207 Epigenetics, 718 Excitatory postsynaptic potentials (EPSPs), 5F-APINACA N-(4-hydroxypentyl), 985 Epilepsy, 437, 607, 796. See also Epileptic Fatty acid amide hydrolase (FAAH), 283, 632 seizures Excitotoxicity, 803, 804, 829 510, 556, 594, 609, 619, 675, 724, risks/benefits, 432 Executive functions (EF), 47, e55, e59, 940, 948 enzyme inhibitors, 63 cannabis safe and well tolerated in e65–e67, 71, 152, 153, 262 FAAHinhibitor URB597, 445 patients, 437 impairment of, 144 pharmacological blockade Exhaled breath colonic propulsion, delay in, 950 pro- and anticonvulsant effects of, 434 after smoking of cannabis GI transit, delay in, 950 compounds in established epilepsy, Fatty acid derivatives, 655 434–436 mean concentration of THC, 1022 FDA. See Food and Drug Administration people without epilepsy, 434 after smoking of THC (FDA) Feddan, 113 seizure, pathophysiological basis of, THC, individual concentration, 1021 Federal Analogue Act, e155 432–434 alcohol testing, use for, 1019 Feeding behavior, 643 amphetamine presence, 1018 Feeding inhibitors, 646 syndromes, 436 analytical aspect, 1022 FEP. See First-episode psychosis (FEP) treatment, 608 cannabinoid presence, 1018 FES. See First-episode schizophrenia (FES) Epileptic seizures, 432, 433, 436 cannabinoid, studies on, 1021–1022 FEV1. See Forced expired volume in 1s cannabis use and effects, 435 collection (FEV1) clinical signs and symptoms, 432 FFT. See Functional family therapy (FFT) first seizures, stratification of, 433 electrostatic filter technology, 1019 F2F treatment. See Face-to-face (F2F) treatment algorithm, 434 component collection treatment Episodic memory, 71 Fibromyalgia, e159 Epoxyeicosatrienoic acid (EETs), 621 tenax tube, use of, 1019 pathogenesis, e159 EPS. See Extrapyramidal side effects (EPS) drug testing symptoms, e159 EPSPs. See Excitatory postsynaptic potentials treatment, e160 liquid chromatography-mass nonpharmacological therapies, e160 (EPSPs) spectrometry (LC-MS), use of, 1019 pharmacological therapies, e160 EQ-5D health survey, 934 Fibromyalgia (FM), 824, 872 ERα. See Estrogen receptor α (ERα) sampling device, 1020 Fibromyalgia Impact Questionnaire (FIQ), ERK. See Extracellular-signal-regulated workflow, 1023 e163 drug testing, use for, 1019 FIQ. See Fibromyalgia Impact Questionnaire kinases (ERK) 11-hydroxy-THC presence, 1019 (FIQ) EROD assay. See 7-Ethoxyresorfin O- lipid, presence of, 1019 First cannabis use, univariate logistic nonvolatile component, presence regression, 975 deethylase (EROD) assay First-episode psychosis (FEP), Escitalopram, 943, 1032, 1071 of, 1019 e55, 257 ESPAD. See European School Survey Project on particle, presence of, 1019 adherence and functionality, 260 protein, presence of, 1019 cannabis use and adherence, 260 Alcohol and Other Drugs (ESPAD) sampling, 1022 cannabis use and functionality, 261 Estrogen, 672 cannabis use as a risk factor for Estrogen receptor α (ERα), 724 collection time, 1022 psychosis, 258 Estrogen signaling pathways, 726 exhaled breath condensate, 1022 high rate of cannabis use among, 258 Ethanol, 665 impactor technology, 1022 impact of cannabis use on cognitive Ethnicity, 83, 84 specimen for functioning in, 262 Ethological models, e144 drugs of abuse testing, 1019 influence of cannabis use on clinical and 7-Ethoxyresorfin O-deethylase (EROD) toxicology investigation, 1019 functional outcomes, 259 THC presence, 1018 role of depressive symptoms in, 259 assay, 814 carboxylic acid, 1019 structural magnetic resonance studies comparison of Ki values for inhibition, 815 Exogenous cannabinoid in patients and cannabis inhibition, kinetic parameters for, 815 CB1 receptor stimulation, 284 use, e56 Ethylenediaminetetraacetic acid (EDTA), 766 Experimental autoimmune encephalopathy treatment for cannabis users, 263 ETM. See Elevated T-maze (ETM) ventricular alterations in cannabis users Euphoria, 122 (EAE), 673 with, e59 Eurobarometer telephone-based survey, 199 Explanatory models, 366 First-episode schizophrenia Europe (FES), e55 age as a predictor of cannabis use, 34 lower vulnerability hypothesis, 368 First synthetic cannabinoids, emphasis on cannabis control, 38 neuro-protection hypothesis, 366 chemical structures, 841 past month cannabis use by age group and social hypothesis, 368 FLAIR imaging, 491 Explicative hypothesis country, 37, 40 of cognitive functioning related to cannabis past year cannabis use by age group, 39 percentage of past year cannabis use by age use in psychotic disorders, 48 Ex situ conservation in gene banks, 8 group, 36 Externalizing disorders, 133 European Medicines Agency (EMA), Extracellular domain, 558 Extracellular-signal-regulated kinases (ERK) e160, 651 European Monitoring Centre for Drugs and cell differentiation, role in, 865 phosphorylation, 566 Drug Addiction (EMCDDA), 25, 33, Extrapyramidal side effects (EPS), 327 e170, 841, 972, 984, 1078 Extrinsic sensory neurons, 473

Index 1129 Fluorescence resonance energy, 579 Gastroesophageal reflux disease (GERD) Geographical distribution, 3, 8 Fluoxetine, 943, 1033, 1071 cannabinoid, effect of, 953 Geranyl diphosphate, 14 Fluvoxamine, 814 mechanism fMRI. See Functional magnetic resonance transient lower esophageal sphincter biosynthesis of, 16 relaxations (TLESRs), 953 GERD. See Gastroesophageal reflux imaging (fMRI) symptom Focal cerebral ischemia (FCI), 407 heartburn, 953 disease (GERD) Food and Drug Administration (FDA), regurgitation, 953 German version of the auditory verbal retrosternal pain, 953 e103, 941 learning test (VLMT), 888 Food intake, 473 Gastrointestinal (GI), 472 Germplasm Resources Information Network Forced expired volume in 1 s (FEV1), 496 inflammation Forced swimming test, 964 endogenous cannabinoids, role of, 951 (GRIN) database, 8 Forced vital capacity (FVC), 496 exogenous cannabinoids, role of, 951 GH. See Growth hormone (GH) Fourier transform infrared spectroscopy TRP channel, role of, 962 GHB (gamma-hydroxybutyrate), 172 motility, 474 Ghrelin (GHRL), 643, 780 (FT-IR) cannabinoid, effect of, 949–952 functional group determination, 985 motor function basal levels, 643 Fractional anisotropy (FA), 347, 393 cannabinoid, effect of, 948 central administration, 644 Friends, influencing marijuana use, 190 cisplatin-treated rat interaction with peripheral CB1 early adolescence, 190 WIN55, 212-2, effect of, 954 early adulthood, middle adulthood, endocannabinoid system receptors, 644 role of, 951 receptors, 644 and beyond, 193–194 targetting drug, effect of, 952 GHRH. See Growth hormone releasing emerging adulthood, 192–193 extrinsic neural control, 951 late adolescence, 191 muscle contraction hormone (GHRH) late childhood, 190 CB1receptor agonists, effect of, 949 GHRL. See Ghrelin (GHRL) middle adolescence, 191 origin, cannabinoid involvement in visceral GI. See Gastrointestinal (GI) Frontotemporal dementia (FTD), 829 pain, 443 Gilles de la Tourette syndrome (GTS), 884 FTD. See Frontotemporal dementia (FTD) Functional family therapy (FFT), 1049 Gastrointestinal (GI) tract, 442, 948 alternative forms of treatment, 885 Functional implications, of cannabis use, small/large intestine, 444 cannabinoid based medicines (CBMs), stomach, 444 155–156 treatment with, 885, 886 Functional magnetic resonance imaging Gatehouse project (GP), 1081 adverse effect, 890 GC. See Gas chromatography (GC) cannabinoids, treatment with, 885, 886 (fMRI), e135, 270, 361, 940 GC-MS. See Gas chromatography mass performance-enhancing effect, 887 cognitive process, neural activation, 270 Cannabis sativa, treatment with, 886–887 FVC. See Forced vital capacity (FVC) spectrometry (GC-MS) case report, 886 GDS. See Global Drug Survey (GDS) controlled trials, 887 G Gene–environment interaction (GxE), e31, 426 prospective survey, 887 Gene expression, 714 causes GABA. See γ-Aminobutyric acid Generalized anxiety disorder (GAD), environmental factor, 884 (GABA) multiple genetic susceptibility factor, e161, 304 GABAergic inhibition, 635 General substance use, common liability quantitative effect of, 884 GABAergic interneurons, 536 comorbid condition GABAergic neurons, 824 to, 177 GABAergic pathways, e144, 721 Genetic and environmental risk factors attention deficit hyperactivity disorder GABAergic transmission, 374, 833 (ADHD), 884 Gabapentin, e161, 943, 1033, 1071 (GxE), 336 Gabapentinoids, e161 Genetic confounding, 426 obsessive compulsive behavior GABA receptors, 771 Genetic markers, for forensic (OCB), 884 allosteric modulation, 774 identification, e7 diagnosis, 884 global CNS elevation, 772 Genetic mouse models, 338 etiology, 884 tiagabine-induced, 774 Genetic polymorphisms, 585, 714 fatty acid amide hydrolase (FAAH) GAD. See Generalized anxiety disorder Genetics, of Cannabis, 7 “Gene x environment” (GxE) interaction inhibitor, effect of, 887 (GAD) features GαI protein coupling, 566 model, 82 Galvanic skin-conductance response, Genitourinary tract, 445 motor tics, 884 vocal tics, 884 320, 321 endometrium, 446 pathophysiology, 884 Gamma-aminobutyric acid (GABA), 62–64, kidney and ureter, 445 endocannabinoid system and ovary, 445 e161, 1033 prostate, 446 neurotransmitter pathways, role Ganja goo ball, e15 testes and scrotum, 446 of, 885 Gas chromatography (GC), 982 urinary bladder and urethra, 445 imbalances in the dopaminergic (DA) Genome, of Cannabis sativa, 7 system, 884 drugs of abuse analysis, 982 Genome-wide association studies cortico-striato-thalamo-cortical (CSTC) Gas chromatography mass spectrometry circuitry, 884 (GWAS), 585 THC, treatment with, 887–888 (GC-MS), 239, 982, 999 Genotypes and chemical phenotypes of adverse effects, 888 golden standard for qualitative randomized controlled trials, 888 cannabis, e7 uncontrolled single case study, 887 analysis, 985 Genotyping, 585 treatment, practical aspect, 890–891 GASP1. See GPCR-associated sorting protein Genuine cannabis allergy, 521 treatment strategies, 885 alternative medicine, 885 1 (GASP1) behavioral therapy, 885 Gastric emptying, ∆9-tetrahydrocannabinol, deep brain stimulation, 885 pharmacological therapy, 885 effect of, 950

1130 Index Herbal cannabis, THC and CBD levels, 25 Herbal smoking blend. See also Smoking GIRK. See G-protein-coupled inwardly- Gray matter (GM), e54, e55, 153 rectifying K+ channels (GIRK) brain structural analysis displaying synthetic cannabinoid, use of clusters of significant decreased chemical structures, 844 GI tract. See Gastrointestinal (GI) tract gray matter, e58 Glandular trichome, e3 Herbal smoking mixture, 840 Glaucoma, 749, 761 GRK. See GPCR kinase (GRK) hERG potassium channel assay, 653 Grooved pegboard test, 376 Heroin self-administration intraocular pressure, 749 Growth hormone (GH), 643 intraocular pressure lowering, 761 Growth hormone releasing hormone effect of CBD, 941 retinal neuroprotection, 762 Heterocycles, 655 treatment, 749 (GHRH), 645 Heterodimerization, 574, 579, 725 Glial fibrillary acidic protein (GFAP), e105 GSK-3β. See Glycogen synthase kinase Heteromers, 579 Glial tumors, e112 Heterosynaptic LTD, 633 multimodal action of cannabinoids 3β(GSK-3β) HETEs. See Hydroxyeicosatetraenoic acid GTS. See Gilles de la Tourette syndrome against, e117, e118 (HETEs) antitumoral action of cannabinoids in (GTS) Hexanoyl-CoA synthetase, 15 GTS-CGI. See Tourette’s syndrome clinical HFS. See High frequency stimulation (HFS) vivo, e117 5-HIAA. See 5-Hydroxyindoleacetic acid effects of cannabinoids on angiogenesis, global impression scale (GTS-CGI) Guanine-nucleotide-binding proteins (5-HIAA) cell migration, and invasion, High Ambiguity Driven DOCKing e118–e119 (G-proteins), 558 Glioblastoma multiforme (GBM), e112, 866 Gut disorder, cannabis, use of, 948 (HADDOCK), 685 cannabinoid, effect of, 866 GWAS. See Genome-wide association studies Higher exposure, to THC and risk of adverse expression of CB2 receptor in human glioblastoma, e113 (GWAS) health effects, 28 Gliomas GxE. See Genetic and environmental risk Higher potency cannabis, and plasma THC alterations of major components of cannabinoid system in, e113 factors (GxE) levels, 26 cell culture Highest occupied molecular orbital cannabinoid, effect of, 866 H therapeutic potential of cannabinoids (HOMO), e124 against human gliomas, e119 Habit formation High frequency stimulation (HFS), 633 results from a pilot clinical associative memory processes, role of, 269 High-resolution computed tomography study, e119 neuroscience of dual systems, role of, 269 risks and constrains, e119 (HRCT), 497 safety profile of therapeutic Habitual cannabis, 66 High resolution mass spectrometry cannabinoids, e119 HADDOCK. See High Ambiguity Driven Global burden of disease (GBD), 90 (HR-MS), 983 Global drug survey (GDS), e187 DOCKing (HADDOCK) advantage, 983 Globus pallidus, 918 HADS. See Hospital Anxiety Depression Glucocorticoid, 672 nontargeted compound, data-dependent Glucose homeostasis, 782 Scale (HADS) acquisition of, 983 Glutamate, 321, 425 Hallucinations, 44, 80 Glutamate receptors, 631 Haloperidol, 330, 862 metabolic patterns of synthetic Glutamatergic neuronal system, 330 Harvey–Bradshaw index, 933 cannabinoid, use in, 983 Glutamatergic neurons, 330 Glutamatergic synapses, 330 result, 935 urine biomarker identification, use in, 983 Glutathione peroxidase (GPx) Hashish during 18th–20th Centuries, 111 Hippocampus, e54, 71 enzymes, 782 HBCC. See Human breast cancer cell (HBCC) Histomorphometric study, in rats Glycogen synthase kinase 3β(GSK-3β), 805 HBSC. See Health behavior in school-aged Goza, 113 activity of osteoblasts, e75 GPCR. See G protein-coupled receptor children (HBSC) bone formation, e75 (GPCR) HD. See Huntington’s disease (HD) bone inflammation around teeth, e76 GPCR-associated sorting protein 1 Head and neck cancers bone loss, during ligature-induced (GASP1), 560 GPCR kinase (GRK), 566 alcohol and tobacco use, e96 periodontitis, e76 GPR55, orphan G-protein linked mutagenic effects of, e96 bone resorption, e75 receptor, e114 risk factors, e97 bone-to-implant contact, reduction in, e76 G-protein-coupled inwardly-rectifying K+ cannabinoid receptors (CB1 and CB2), channels (GIRK), 560 case-control study in, Boston, e96 G-protein coupled receptor (GPCR), 558, 565, INHANCE Consortium, e97 activation, e75 574, 584 marijuana use and, e96 cannabis smoke inhalation, e76 allosteric modulation, 574 cannabis smoking, cancellous bone healing signaling, 683 epidemiological studies, e98 G protein coupling promiscuity, 568 potential relation, e96 impact of, e73 G-proteins. See Guanine-nucleotide-binding sexual behavior, confounding by, e96 degree of bone-to-implant contact, e73 proteins (G-proteins) Health behavior in school-aged children effect of marijuana inhalation, e76 GPx enzymes. See Glutathione peroxidase endocortical osteoblast number, (GPx) enzymes (HBSC), e187 Health risk, 30 enhancement, e76 Healthy life style trial furcation region of rat molar, e77 immune targets, cannabinoid-based tobacco smokers with psychosis, e207 Heart, 441 drugs, e75 periodontal inflammation, regulation disease, 489 HEIA. See Homogeneous enzyme of, e76 periodontitis, effects of cigarette immunoassay (HEIA) Heme oxygenase-1 enhanced portal smoking, e73 photomicrographic illustration, bone hypertension, 513 Hemp, e2, e4, e5 healing in implant surface, e74, e75 retention device for, oral varieties, 8 Hepatic CYP isozymes, 437 microorganisms, e76 Hepatic stellate cells (HSCs), 506

Index 1131 risk factor for, e76 Hydrophilic prodrug derivatization, 766 Illegal recreational drug tetrahydrocannabinol (THC) detection in, Hydrophobic interactions, 685 cannabis, 940 11-Hydroxy-delta 9-tetrahydrocannabinol stimulant, 940 urine samples, e75 THC effect in, inhibiting CB2 (11-OH-THC), 1010, 1011, 1013 Illicit Drug Reporting System (IDRS), 104 6-Hydroxydopamine-induced apoptosis, 920 Illicit drugs, e12, 131, 161, 171, 201 expression, e76 6-Hydroxydopamine lesioned rat, Illness-inducing agent, 705 thirty Wistar rats, e73 Imidazopyridines, 602 titanium implants, decrease bone mass 920, 922 Immune cells, 559 Hydroxyeicosatetraenoic acid (HETEs), 621 Immune thrombocytopenic purpura around, e73, e75 5-Hydroxyindoleacetic acid (5-HIAA), 706 HIV painful neuropathy (HIV-PN), 911 Hydroxylation, 238 (ITP), 587 HIV-PN. See HIV painful neuropathy 5-Hydroxy-l-tryptophan (5-HTP), 329 Immunoallergic vasculitis, 490 N-(4-Hydroxyphenyl)-arachidonamide, 920 Immunoassay screening (HIV-PN) Hydroxypropyl methyl cellulose (HPMC), 1H-MRS. See Proton magnetic resonance urine screening, 982 766 Immunocytochemical analyses, 559 spectroscopy (1H-MRS) 11-Hydroxy-THC (11-OH-THC), 238 Immunohistochemical analyses, 444 Homicide rates, 127 5-Hydroxytryptamine (5-HT), 329 Immunohistochemistry, e113 HOMO. See Highest occupied molecular 5-Hydroxytryptamine1A (5-HT1A) Immunological methods, 239 Immunosuppression, 437 orbital (HOMO) receptors, 704 Implicit association test (IAT), 269 Homodimeric enzyme, 15 agonists, 706 Homogeneous enzyme immunoassay antagonists, 706 attitude examination, 269 Hyperalgesia, 906 behavior-related associative memory (HEIA), 988 Hyperemesis, 467 Homosynaptic LTD, 634 Hyperglycemia, 780 structure, examination Homovanillic acid elevation, 282 Hyperpolarization, 577 of, 269 Homozygous THC producing BtBt Hypertelorism, 163 imaging, 270 Hyperthermia, e105 INCANT. See International cannabis need of genotypes, 8 Hypocretinergic system, 538 treatment trial (INCANT) Hopkins verbal learning test, 1088 Hypocretin system, 534 Incarceration, 124 Hospital Anxiety Depression Scale (HADS), addictive properties of drugs abuse, Incidence rate ratio CapOpus group e162 role in, 535 vs. TAU, 1089 HPA. See Hypothalamic-pituitary-adrenal cannabinoid dependence, role in, 538 Incompatible trial mRNA levels, 538 regions of activity within group, 274 axis (HPA) potential therapeutic utility, 536 Indole, 593 HPMC. See Hydroxypropyl methyl cellulose Hypokinesia biological data, 595 haloperidol-induced, 887 chemical structures, 596 (HPMC) Hypolocomotion, 741 Indoor cultivation, of C. sativa, 9 HPT-axis. See Hypothalamic-pituitary- Hypomania, 422 Inducible nitric oxide synthase Hypomotility, 651 (iNOS), 963 thyroid axis (HPT-axis) Hypothalamic-pituitary-adrenal axis Inferior colliculus (IC), e141 HRCT. See High-resolution computed Inflammatory bowel disease (IBD), 475, 932, (HPA), 279 953, 962 tomography (HRCT) long-term cannabis use, effect cannabis, treatment with, 918 HR-MS. See High resolution mass beneficial effects, 921 of, 952 hospitalization risk, 922 spectrometry (HR-MS) Hypothalamic-pituitary-thyroid axis side effect, 922 HSCs. See Hepatic stellate cells (HSCs) surgery risk, 922 5-HT. See 5-Hydroxytryptamine (5-HT) (HPT-axis), 462 cannabis user vs. nonusers of cannabis, 5-HT1A receptors. See 5-Hydroxytryptamine1A Hypothermia, 651, 741 922, 927 Hypoxic-ischemic brain injury, 803 Crohn disease (CD), 954 (5-HT1A) receptors patient, beneficial effects of cannabis, 925 5-HTP. See 5-Hydroxy-l-tryptophan (5-HTP) I treatment HU-210, 920 inhaled cannabis, 921 HU-308, 920 IBD. See Inflammatory bowel disease (IBD) option, 932 Human breast cancer cell (HBCC), 723 IBS. See Irritable bowel syndrome (IBS) self-administration of cannabis, 921 Human bronchial pathology, 498 Ibuprofen, 824 ulcerative colitis (UC), 954 Human colon adenocarcinoma cell line IC. See Inferior colliculus (IC) Inflammatory steatohepatitis, 587 ICD. See International classification of Inheritance of chemical phenotype, in HT29 CBG, 960 C. sativa “codominant monogenic Human functional imaging technique, 270 diseases (ICD) control, ”, 8 Human ghrelin, chemical structure, 643 ICD-10 criteria, 1087 Inhibition, 152, 153, 156 Human in vivo neuroimaging techniques, 346 ICH. See Intracerebral hemorrhage (ICH) iNOS. See Inducible nitric oxide synthase Human motor cortex, 374 ICSS paradigm. See Intracranial self- (iNOS) Human studies, 506 In situ conservation as in vitro gene Human trials, 749 stimulation (ICSS) paradigm banks, 9 Humulus lupulus (hop), 14 IgE-mediated reaction, 518 Insomnia, 824 Huntington’s disease (HD), 405, 434, marijuana, use of, 872 primary, 518 806, 829 principles, 518 cannabinoid signaling, 924 secondary, 518 characteristic ILAE. See International League Against behavioral deficits, 918 Epilepsy (ILAE) cognitive, 918 Ill-being, cannabis, 311 motor dysfunction, 918 Illegal drug usage, e155 effect of cannabinoids, 924 clinical data, 924 genetic model, 926–927 effect of cannabinoids, 927 Hydromorphone, 771

1132 Index Instrumental conditioning, 318 Ionization potential (IP), e124 Legislation, 239 Instruments, for assessing premorbid Ionomycin, 962 approaches to, 239 Iowa gambling task (IGT), 293 Australia, 240 IQ, 226 Canada, 240 Instruments selection performance, differences in European Union, 240 between chronic marijuana users and impairment legislation, 239 from the literature, e170–e171 control, 294 United States, 240 Intellectual quotient (IQ), 224 zero-tolerance laws, 239 PET activation, differences in Flynn–Dickens model, 227 between chronic marijuana users and Lennox–Gastaut syndrome, 436, 799 longitudinal studies on premorbid IQ, control, 294 Leonotis leonurus, 840 Leonurus sibiricus, 840 227–229 IP. See Ionization potential (IP) Levonantradol, 862 premorbid IQ and cannabis IQ scores, e59 Leydig cell, 965 Irritable bowel syndrome (IBS), 953 LFP. See Local field potential (LFP) findings from longitudinal Libido, 181 studies, 229 characteristic Life satisfaction, 289 abdominal discomfort, 954 Life skills training (LST), 1078, 1082 risk, 229–231 altered bowel habits, 954 Likert-type scale, 1028 Intensive forms, of drug use, 973 bloating, 954 Limbic-motor interface regulating stress Internalizing disorders, 133 International cannabis need of IRT analysis. See Item response theory (IRT) response, 872 analysis Limits of detection (LOD), 854 treatment trial (INCANT), 1048, Lipopolysaccharide (LPS), 405 1050, 1051 Ischemia, 407 Lipoxin A4, 579 flow diagram, 1051 reperfusion injury, 507 Lipoxygenases (LOX), 621 outcomes, 1051 treatment site characteristic, 1050 Ischemic ulcers, 483 pathway, 15 International classification of diseases (ICD), Islets of Langerhans, 780 Liquid chromatography (LC), 982, 986, 995 90, e170, 299 Item response theory (IRT) analysis, 318 International League Against Epilepsy ITP. See Immune thrombocytopenic purpura aqueous biological sample analysis, 982 (ILAE), 607 bioanalysis, 982 International Lung Cancer (ITP) Liquid chromatography coupled to mass Consortium, e95 Interpersonal predictor, 1041–1042 J detector (LC-MS or LC-MS/MS), family influence, 1042 239, 999, 1019, 1022 peer influence, 1041 Jam band performance, e14 Literatures Interpretation of result, 1014–1015 Joints, e169 regarding impairment after long-term use historical use, 1015 JWH-018, 841 of cannabis, 29 medicinal use, 1015 JWH-081, 982 regarding impairment of acute cannabis proof of use, 1015 JWH-122, 982 effects, 28 recent use, 1014 JWH-210, 982 Lithium, 1071 Inter simple sequence repeat amplification JWH chemical compounds, e153 Lithium carbonate, 1031 (ISSR), e7 Liver, 444 Intervention, 1087–1088 K disorders, 587 CapOpus trial, 1087–1088 Liver cirrhosis treatment as usual (TAU), 1088 Kaempferol, 814 effect of cannabinoids, 510 Intervention design Kainic acid model, 611 hemodynamic changes, 512 marijuana use reduction, 1104 Karyotype, e4 Local field potential (LFP), 797 Intervention group Keratinocytes, 453, 544 LOD. See Limits of detection (LOD) time to first psychiatric emergency room Lofexidine, 1031, 1032, 1071 contact, 1090 atopic-like inflammation, regulation Longitudinal studies, 35 time to first psychiatric hospital of, 547 on premorbid IQ, 227–229 contact, 1091 Long-term depression (LTD), 714, 734 Intestinal inflammatory condition endogenous cannabinoid system, 544 Long-term marijuana use. See also Marijuana cannabinoid, effect of, 953–955 proinflammatory chemokines, secretion brain, effect on, 874 Intoxications, 224, 433 Long-term potentiation (LTP), 714, 734 Intracerebral hemorrhage (ICH), 488 of, 546 Long-term video-EEG, 436 Intracranial self-stimulation (ICSS) paradigm, Ketamine, 172, 173, 175, 636, 790 Lorcaserin, 650 660, 941 Ketoprofen, 453 Lower GI tract, functional disorders, 474 Intraocular pressure, 749 Khat plant, e103 Lower urinary tract symptoms (LUTS), 441 cannabinoid-induced reduction, cellular K2/Spice, synthetic cannabinoids, 441, 849 Lower vulnerability hypothesis, 368 mechanisms, 755 Kupffer cells, 513 Lowest unoccupied molecular orbital ciliary epithelium, 755 (LUMO), e124 trabecular meshwork, 755 L LSD (lysergic acid diethylamide), 172 Intrapersonal predictor, 1038–1039 LSEQ. See Leeds Sleep Evaluation cognitive processing, 1039 l-α-Lysophosphatidylinositol (LPI), 407 Questionnaire (LSEQ) neurobiological, 1038–1039 Lapse situation LST. See Life skills training (LST) self-image and deviant behavior, 1039 LSV. See Lateral septum (LSV) In vitro micropropagation of leaf-derived intervention strategy, 1061–1062 LTD. See Long-term depression (LTD) calli from C. sativa L., 10 Lateral septum (LSV), 339 LTP. See Long-term potentiation (LTP) Ion channel transient receptor potential A1 Laxatives, 123 (TRPA1), 445 LC. See Liquid chromatography (LC) Learning theory, 318 Leeds Sleep Evaluation Questionnaire (LSEQ), e165 Left inferior frontal gyrus, 270 Legal considerations, 124 Legal drugs, e153 Legal highs, e151, 841, 854

Index 1133 LUMO. See Lowest unoccupied molecular legalization, 1102 Maternal breast milk, 529 orbital (LUMO) in the United States, 195 Matrix metalloproteinase 2 (MMP-2) Lung adenocarcinoma motherhood, legal concerns, 531 activity, 509 mice animal model, 865 physiological effects, 482 Maximal finger tapping, 375 picture, 271 MCF-7 cells, 724 Lung cancer, 498 polydrug use, 1102 MD. See Molecular dynamics (MD) and alcohol use, e81 primary care, brief treatment, 1102 MDA. See Malondialdehyde (MDA) case control study in New Zealand, e82 recreational use, 1102 MDFT. See Multidimensional family therapy data from, Maghrebian region, e95 smoker, 1019 family history, e82 smoking, in form of blunts within hip-hop (MDFT) histological changes in, tracheobronchial MDMA. See 3, 4-Methylenedioxymetham- epithelium, e82 subculture, e12, e13 logistic-regression models, e95 structural brain change, 1102 phetamine (MDMA) marijuana use in late adolescence/early substance use disorder, 1102 MDMA (3, 4-methylenedioxy-N- adulthood, e81, e95 and tobacco use, e81 epidemiological studies, e98 trajectories, use for those in early methylamphetamine), 172 risk of, e95 reinforcing effects, e105 and tobacco use, e81 adulthood, 193 Mean diffusivity (MD), 393 treatment project, 1030 Meconium, 162 M usage, e81 Median raphe nucleus (MRN), 705 Medicago sativa, 15 Mad hatter, 988 adolescent, 1102 Medical cannabis, 34 MAGL. See Monoacylglycerol lipase among jazzmen, e12 well being, direct effect on, 310 behavioral study, 269, 1102 well being, indirect effect on, 310 (MAGL) contextual factor, 1102–1103 Medical marijuana, 869–871. See also Magnetic resonance imaging (MRI), e59, 433 disorder, 871 Magnetic resonance spectroscopy (MRS), effect Marijuana acute immune deficiency syndrome 350, 375 apathy, 289 in cannabis use, 351 lack of motivation, 289 (AIDS), effect on, 870 in early psychosis, 351 lethargy, 289 antiemetic properties, 870 Main myenteric neuronal population habit-related change, 274 central nervous system effect, 870 endocannabinoid system, components implicit association toward, 271 epilepsy, effect on, 870 intervention insomnia medicine, 870 of, 950 counseling plus mobile technology, mental disorder, effect on, 871 Major depressive disorder (MDD), 300, 310 multiple sclerosis (MS), effect on, 870 Major histocompatibility complex use of, 1104 short-term physical effect, 870 mean momentary desire, 1107 Medication, 823 (MHC), 894 momentary factor, 1102–1103 compliance, 203 Malignant cardiac arrhythmia, 482 performance on a motivational task, 294 Medicinal properties, of cannabis Malondialdehyde (MDA), 782 positive subjective-effect rating, increase Malonyl-CoA, 15 plant, 451 Manchester short assessment of quality of life in, 1102 Medicines and Healthcare Products sense of euphoria production, 1102 (MANSA), 1088 social anxiety, effect of, 1103 Regulatory Agency (MHRA), 822 Mania, 422 social environment, effect of, 1103 Mental health Manolis study from 1983, 1019 young adult, 1102 MANSA. See Manchester short assessment of user vs. nonuser, 269 human endocannabinoid system, effect withdrawal symptoms, 871 of, 301 quality of life (MANSA) Marijuana-IAT imaging, 270–271 MAPKs. See Mitogen-activated protein incompatible trial Mental illness temporal layout of, 272 cannabis use, cooccurrence with, kinases (MAPKs) inferior frontal gyrus, 272 299–302 Marijuana, e2, 3, e12, 25, 39, e80, 162, 181, 189, interaction effect, 273 cross-sectional data, 302 orbitofrontal cortex, 272 cannabis user, 301 194, 481, 527, 730 paradigm, 271–274 concurrent cannabis use abuse, 1070 Marijuana plant mechanism, 301 and alcohol use, e81 cannabidiol (CBD), 872 prevalence of cannabis use, 300 Cannabis sativa, 440 delta-9-tetrahydrocannabinol (THC), 872 cardiovascular consequences, 482 Marijuana substitute, 840 5-MeODMT. See 5-Methoxy-N, N- bay bean, 840 dimethyltryptamine (5-MeODMT) cardiomyopathy, 482 blue lotus, 840 cerebrovascular effects, 483 honeyweed, 840 6-Mercaptopurine, 932 myocardial infarction, 482 Indian warrior, 840 Meristemoid formation, 10 myocardial ischemia, 482 lion’s tail, 840 Mesolimbic dopamine system, 289 peripheral vascular disease, 483 maconha brava, 840 Mesolimbic/mesocortical DA system, 282 cigarette, 818 Marinol, 862, 1010 MET. See Motivational enhancement consumption, 181 Mass spectrometry (MS) desire, 1102 clinical application, 982 therapy (MET) detection in biological specimen, 1008 forensic analysis, 982 Metabolic disturbances, 433 development of cancer, e81 Mast cell, 932 Metabotropic glutamate receptors electronic dance music (EDM), e15–e16 Master’s-level university librarian (TF), e81 eligible articles, e81 (mGluRs), 631 friends impact use, 189 METH. See Methamphetamine immunoassay test, 982 Methadone, 940 inhalation route, 527 jam band subculture, e14–e15 improved substance abuse outcome, 940 Methadone induction, 874 Methamphetamine (MA), 48, 172, 181, 373, 941

1134 Index Methamphetamine (METH), e102 Microscopic photographs of C. sativa Momentary self-monitoring and feedback + annual prevalence of, in United States, e103 trichomes, 5 motivational enhancement as crystal/chalk/ice, e103 therapy (MOMENT) intervention, dopaminergic neuronal activity, e104 Midazolam, 775 1103–1108 Midbrain tectum (MT), e143 Methionine (Met) allele, 418 Migration phenomena, 83 component, 1103, 1104 Methodological limitations, 50 design, 1104 Methotrexate, 932 cannabis use, and psychosis formative research, 1104 5-Methoxy-N, N-dimethyltryptamine onset, 85 MET sessions (5-MeODMT), 329 causing psychotic disorders, 84 field note, 1107 Methylenedioxymethamphetamine (MDMA), risk factors for first episode psychosis mobile technology, use of, 1104 momentary reporting, 1105 e12, e15 in migrants, 85 pilot study, 1104 3, 4-Methylenedioxymethamphetamine risk of first episode psychosis (FEP) data collection, 1105 (MDMA), e15, 655 in populations, 84 pilot study phase cathinone, e103 types of, 83, 84 consumption, e104 Military substance use, e154 momentary, daily, and individual dopaminergic neuronal activity, e104 media coverage, e154 outcome dopaminergic stimulation, e103 Milnacipran, e161 dysphoric symptoms of, ecstasy, e103 Mineralocorticoid, 672 differences in, 1106 psychostimulant drugs, e103 Miniature inhibitory postsynaptic currents individual-level mean, 1106 in synthesis of styptic drugs, e104 standard deviation, 1106 Methylphenidate, 771, 885, 941 (mIPSCs), 578 potential challenges to implement, 1108 1-Methyl-4-phenyl pyridinium [MPP(+)] mIPSCs. See Miniature inhibitory randomized controlled trial, 1105 induced cell death, 920 responsive messaging, 1105 1-Methyl-4-phenyl-1, 2, 3, postsynaptic currents (mIPSCs) Monoacylglycerol lipase (MAGL), 283, 340, MIS. See Multifocal arterial stenosis 6-tetrahydropyridine (MPTP) 556, 609, 618, 631, 948, 960 neurotoxic effect, 920 (MIS) Monoamines dopamine (DA), e103 Metochlopramide, 862 MIST. See Montreal imaging stress task Monocyclic cores, 597 MGL. See Monoacylglycerol lipase (MGL) mGluRs. See Metabotropic glutamate (MIST) biological data, 596 Mitochondria dysfunction, 831 chemical structures, 597 receptors (mGluRs) Mitogen-activated protein kinases pyridines, 598 MHC. See Major histocompatibility complex pyrimidines, 598 (MAPKs), 452, 560, 632, 682 sulfamoyl benzamides, 598 (MHC) MMP-2 activity. See Matrix metalloproteinase Monte Carlo simulation, 684 MHRA. See Medicines and Healthcare Montreal imaging stress task (MIST), 2 (MMP-2) activity Products Regulatory Agency Mobile technology 280–281 (MHRA) Mood disorder, 871 MI. See Motivational interviewing (MI) ecological momentary intervention (EMI), Mice xenograft model, 865 delivery of, 1108 cannabinoids, effect of, 864 Michigan alcohol screening test, e181 cannabis, 302–303 Microglia, 674 marijuana use reduction, 1104 course of activation process Modafinil, 941 activated state, 402 Modeling, earlier age of onset of cannabis use, effects of, 303 as active sensors, 402 and insomnia, 864–865 antiinflammatory effects, 404 schizophrenia, 92 marijuana, effect of, 871 cannabinoid receptors, 404 additional burden attributable to serotonergic system, effect of, 864 chemokine-receptor, 404 three-year incidence effector cells, 403 cannabis use as a risk factor expression of “Off” signals, 403, 404 for schizophrenia, 93 lifetime cannabis user motility control depends on ATP, 402 burden of cannabis dependence, 93 vs. nonuser, 302 “On” signals, triggering process, 403, 404 country-level DALYs, 97 proinflammatory genes activation, 403 estimated DALYs attributable to regular tryptophan, effect of, 864 purinergic 2X ionotropic receptors, 403 cannabis use as a risk factor for Morphine, 455 P2Y metabotropic receptors, 403 schizophrenia, 2010, 98 resting state, 402 estimated DALYs for cannabis, by sex and brain reward function signal regulatory protein α (SIRPα) region, 2010, 96 effect of CBD, 941 receptor, 404 estimated prevalence and number toll-like receptors (TLR), 403 of cases of cannabis dependence reward-facilitating effect endogenous cannabinoid system in 2010, by sex and region, 95 effect of CBD, 941 cannabinoid agonists, direct effect of, 405 global cannabis dependence DALYs cannabinoid agonists, direct effect on (all YLDs) by age and sex, 95 Morphine-dependent rodent receptors, 405–407 implications of findings, 96 abstinence scores downstream effector of ECS limitations, 99 effects of CBD, 941 deregulation, 408–410 modelling increased severity of naloxone-precipitated withdrawal, 941 endocannabinoids (eCBs), 405 Schizophrenia, 92 withdrawal in neurodegenerative diseases, 405 pooled regional prevalence of cannabis effects of CBD, 941 hematopoietic origin, 402 dependence, 2010, 94 im central nervous system (CNS), 402 prevalence of cannabis dependence, 92 Morphine withdrawal symptoms proportion of DALYs due to naloxone-precipitated, 874 cannabis dependence relative to, 98 Motherhood, 531 Modulatory sites, 574 Motivation, 319 Molecular classification, 7 Molecular dynamics (MD), 686 for achievement MOLPROBITY, 684 during high school, 290 theory, 291–292 cannabis use, educational under- achievement lead, 292

Index 1135 educational under-achievement, outpatient treatment program, 1053 fibromyalgia, effect on, 880 cannabis use lead, 291 vs. comparison treatment, 1052 synthetic CB1 receptor agonist, 880 Multifocal arterial stenosis (MIS), 487 Nabiximols, 910, 1071 problem behavior theory, 292 Multimodal therapy, 453 NAc. See Nucleus accumbens (NAc) during university, 291 Multiple choice vocabulary test N-Acetyl-aspartate (NAA), 350 cannabis intoxication, effect of, 293 N-Acetylcysteine, 1033, 1071 cannabis use, 310 (Mehrfachwahl-Wortschatztest, N-Acylethanolamine acid amidase chronic cannabis user, 289 MWT-B), 888 laboratory measure, 289, 293–295 Multiple sclerosis (MS), 106, 405, 806, 894, 963 (NAAA), 960 acute effect, 293 antiinflammatory treatment, 895 N-Acylethanolamine-hydrolyzing acid effects of chronic use, 293–295 characteristic marijuana use, effect of, 289 autoimmune disease, 894 amidase (NAAA), 619 research demyelination, 894 N-Acylethanolamines (NAEs), 619 limitation, 292 multifocal inflammation, 894 N-Acyl phosphatidylethanolamine neuronal injury cultural difference, 292 brain, 894 phospholipase (NAPE), 283 multiple forms of substance use, 292 optic nerve, 894 NADA. See N-Arachidonoyl dopamine self-report, 289–290 spinal cord, 894 dopamine examination, 290 chronic inflammatory demyelinating (NADA) Motivational enhancement therapy (MET), disease, 963 NAEs. See N-Acylethanolamines (NAEs) first-line medication NAFLD. See Nonalcoholic fatty liver 135, e195, 1032, 1094, 1103, 1104, glatiramer acetate, 895 1107, 1108 immunomodulatory medication, 895 disease (NAFLD) Motivational index score immunosuppressive medication, 895 NAPE. See N-Acyl phosphatidylethanolamine chronic alcohol user interferon-β, 895 vs. healthy volunteer, 295 microglial activation, 963 phospholipase (NAPE) Motivational inhibitory control, 293 neuropathic pain Naphthoylindoles, 692, 721, 982 Motivational interviewing (MI), e194, 1104 CBD/THC combination, effect of, 899 Naphthoylpyrroles, 721 Motivation enhancement training (MET), patient Naphthylmethylindenes, 692 e203 expanded disability status scale Naphthylmethylindoles, 692 Motor disorders, 824 (EDSS), 894 Naphthylpyrroles, 692 Motor expressions, 607 risk factor Naphthyridines, 602 clonic, 608 environmental, 894 N-Arachidonoyl dopamine (NADA), 510, myoclonic, 608 Epstein–Barr virus infection, 894 tonic, 608 Herpesvirus 6 infection, 894 632, 878 tonic-clonic, 608 multiple genetic, 894 N-Arylamide oxadiazoles, 600 Motor global scale, 888 Theiler’s murine encephalomyelitis virus NASH. See Nonalcoholic steatohepatitis Mouse cerebellar granule cell, 920 (TMEV) model, 963 Mouse model of ileus treatment, 896 (NASH) cannabidiol, effect of, 955 cannabidiol (CBD), use of, 895 Nasopharyngeal cancers, e96 MPP(+). See 1-Methyl-4-phenyl pyridinium sativex compounds, use of, 895 National adult reading test, 1088 [MPP(+)] Multiple substance use, rates of, including National Campaign against Drug Abuse MPTP. See 1-Methyl-4-phenyl-1, 2, 3, cannabis, 174 6-tetrahydropyridine (MPTP) Multisystemic therapy (MST), 1049 (NCADA), 105 MPTP-induced parkinsonism, 921 Multivariate multinomial analysis, 977–978 National Cannabis Policy (NCP), 106 MPTP-marmoset model, 921 Murine colitis National Cannabis Prevention and MPTP-treated rhesus monkey, 921 dinitrobenzene sulfonic acid (DNBS) MRN. See Median raphe nucleus (MRN) model, 963 Information Centre mRNA second messenger, 456 Muscimol, 775 (NCPIC), 107 MRS. See Magnetic resonance spectroscopy Mutagen-activated protein kinases (MAPKs) National Center for Biotechnology (MRS) apoptosis, role in, 865 Information (NCBI), 586 MS. See Multiple sclerosis (MS) Mutation, e3 National comorbidity survey (NCS), 299 MST. See Multisystemic therapy (MST) Myeloperoxidase, 804 National Council for Addiction Treatment MS therapy pipeline, 901 Myenteric neuron and Prevention (NCATP), 119 MT. See Midbrain tectum (MT) endocannabinoid system, relation with, 949 National Drugs Campaign (NDC), 108 Multidimensional family therapy (MDFT), Myocardial infarction (MI), 482, 587 National Drug Strategy Household Survey 1049–1050 Myocardial ischemia, 482 (NDSH), 102, e187 certified therapist National Epidemiologic Survey on requiremen, for, 1053 N Alcohol and Related Conditions effects of, 1050–1051 (NESARC), 299 implementation in Europe, 1051–1054 NAA. See N-Acetyl-aspartate (NAA) National Fibromyalgia and Chronic Pain accreditation, 1051–1052 NAAA. See N-Acylethanolamine-hydrolyzing Association (NFCPSA), e163 innovation, 1053–1054 National Institute on Drug Abuse (NIDA), licensing, 1053 acid amidase (NAAA) 199, 463, 1000 number of team, 1053 Nabilone, 822, 862, 872, 912, 943, 953, 1071 National Registry of Evidence-based team requirement, 1053 Programs and Policies training, 1053 chemical structures, 822 (NREPP), 1078 treatment center manager, 1052 chronic insomnia, effect on, 880 National Survey on Drug Use and Health intervention, 1050 comorbid posttraumatic stress disorder, (NSDUH), e95, e187, 300 National Survey on Mental Health and effect on, 880 Wellbeing (NSMHWB), 301 Nausea, 705 Nausea and emesis cannabinoid, effect of, 953 Nausea and vomiting pathogenesis, 862

1136 Index Navy Drug Screen, e154 Neuropeptide (NPY), 640 Noncontrolled clinical trials, e163 NCBI. See National Center for Biotechnology Neurophysiological tests, 742 Non-F2F treatment. See Non-face-to-face Neuro-protection hypothesis, 366 Information (NCBI) Neuroprotective effect, 49 (non-F2F) treatment NDD. See Neurodegenerative disorders Neuropsychological assessment battery Nongastrointestinal origin (NDD) maze, 1088 cannabinoid involvement in visceral NDSHS. See National drug strategy Neuropsychological deficits, 225 pain, 443 Neuroticism, 310 household survey (NDSHS) Neurotoxicity, 225 Nonmilitary drug use, e155 Nefazodone, 1031, 1032 Neurotransmission, 445, 830 Nonrandomized clinical trials, e163 Neonatal fecal levels, 529 Nonspecific lipid transfer protein (ns-LTP), Neonate, 530 modulation, 830 systems, 66 519 marijuana exposure, long-term effects, 530 Neurotransmitter Nonsteroidal antiinflammatory drugs marijuana exposure, short-term effects, 530 pleasurable experience, 319 NESARC. See National Epidemiologic Survey New psychoactive substances (NPS), e103, (NSAIDs), e161, 441, 624, 730 11-Nor-9-carboxy-∆9-tetrahydrocannabinol on Alcohol and Related Conditions 172, 173, 841 (NESARC) bath salts, e104 (THC-COOH), e189, 238, 1010, Neural network model, 269 discovery of, e103 1011, 1013 Neuregulin 1 (NRG1), 336 exchange-diffusion model, e104 Not for human consumption, e155 Neuroadaptation, 321, 456 indirect monoaminergic agonists, e104 3NP. See 3-Nitropropionic acid (3NP) Neuroanatomical analysis, 348 neurobiological interactions, e103 NPS. See New psychoactive substances (NPS) Neurobiological stimulation, 318 plant fertilizers, e104 NPY. See Neuropeptide (NPY) Neuroblastoma cells, 566, 920 rates of cannabis use in users of, 175 NREPP. See National Registry of Evidence- Neurocognitive abnormalities, 157 reported to the EMCDDA, 842 Based Programs and Policies Neurocognitive deficits, in emerging adult representative packaging of, e104 (NREPP) cannabis, 153 New synthetic cannabinoids, 843 NRG1. See Neuregulin 1 (NRG1) Neurocognitive effects, 152, 157, 224 New Zealand Cancer Registry, e96 NRG1-cannabis interactions, 336, 339 Neurocognitive implications, of cannabis NFCPSA. See National Fibromyalgia and NRG1 signaling pathway, 346 use, 152 NRS. See Numeric Rating Scale (NRS) Neurodegenerative disorders (NDD), 804 Chronic Pain Association (NFCPSA) NRs. See Nuclear receptors (NRs) Neurodevelopmental impairment, 231 NF-kB. See Nuclear factor kappa B (NF-kB) NSAID-induced gastric hemorrhages, 444 Neuroimaging studies, methodological Nicotine, 48, 321, 665 NSAIDs. See Nonsteroidal antiinflammatory limitations of, e50 drugs (NSAIDs) Neuroimaging technique, 250, 320, 375 consumption, 162 NSDUH. See National survey on drug use event-related potentials, 250–251 dependence, Fagerström test, e169 and health (NSDUH) functional magnetic resonance NIDA. See National Institute on Drug Abuse ns-LTP. See Nonspecific lipid transfer protein imaging, 251 (ns-LTP) functional magnetic resonance imaging (NIDA) NSMHWB. See National Survey on Mental (fMRI), 281 Nigrostriatal damage Health and Wellbeing (NSMHWB) positron emission tomography (PET), 281 NTS. See Nucleus of the solitary tract (NTS); Neuroinflammation, 673, 831 6-hydroxydopamine induced See also Nucleus of tractus solitarius Neuroinflammatory disorders, 673 effect of cannabinoids, 921 (NTS) Neuromaturational changes, 157 Nuclear factor kappa B (NF-kB), 733 Neuromodulation, 714 1-methyl-4-phenyl pyridinium [MPP(+)] Nuclear magnetic resonance spectroscopy Neuronal maturation, 346 induced (NMR), 982, 985 Neuropathic pain, 823 Nuclear receptors (NRs), 672 approach to the management, 910 effect of cannabinoids, 922 Nucleus accumbens (NAC), 328, 534, 743 cannabinoids, role of 1-methyl-4-phenyl-1, 2, 3, Nucleus of the solitary tract (NTS), 862 future clinical study, 913 Nucleus of tractus solitarius (NTS), 642 cannabinoids, use of, 864, 909 6-tetrahydropyridine (MPTP) Numeric Rating Scale (NRS), e162 common causes, 906 induced mechanism, 906 effect of cannabinoids, 922 O pathogenesis Nigro-tectal pathway activity, e145 l-glutamate, role of, 864 Nitric oxide (NO), 796 OAS. See Oral allergy syndrome (OAS) pathological process, 906, 907 synthase, 472, 498 Obesity, 473, 650 diabetic polyneuropathies, 906 3-Nitropropionic acid (3NP), 806 Obsessive compulsive disorder (OCD), e132 postherpetic neuralgia, 906 NK cell, 932 OCD. See Obsessive compulsive disorder postsurgical/traumatic neuropathies, 906 NMDA. See N-Methyl-d-aspartate (NMDA) spinal cord injury, 906 NMDA receptor (OCD) trigeminal neuralgia, 906 N-Methyl-d-aspartate (NMDA) Ocular pain and inflammation, 762 pharmacological treatment, 908, 909 induced neuronal death, 873 Ocular tumors, 762 symptoms and sign, 906 receptor, 330, 762, 803 Odds ratio (OR), 92, 211, 212 Neuropathy antagonists, 330 OEA. See Oleoylethanolamide (OEA) diabetic distal symmetrical sensorimotor amantadine, 330 OF. See Oral fluid (OF) polyneuropathy, 912 MK-801, 330 11-OH-THC. See 11-Hydroxy-delta HIV infection, due to, 911 NO. See Nitric oxide (NO) spinal cord injury, 912 Nocturnal motor activity 9-tetrahydrocannabinol THC, effect on, 874 (11-OH-THC) Nonaffective psychosis, 46 Oleoylethanolamide (OEA), 646 Nonalcoholic fatty liver disease Olivetolic acid, 14, 15 (NAFLD), 587 Olivetolic acid cyclase (OAC), 16 Nonalcoholic steatohepatitis (NASH), 587

Index 1137 Olivetol synthase (OLS), 15, 16 sample cannabinoid, effect of, 955 OLS protein, 15 from frequent marijuana smoker symptom Ondasetron, 863 concentration of cannabinoid, 1012 One-leg stand (OLS) test, 851 median concentration of bloating, 955 On-site device cannabinoids, 1013 distension, 955 marijuana positive emesis, 955 cutoffs for cannabis, 1000 cannabinoid composition, 1014 gas and secretion accumulation, 955 sensitivity for, cannabis in oral visceral pain, 955 sativex user Parental communication and children’s fluid, 1002 median cannabinoid ratios, 1015 specificity for, cannabis in oral fluid, 1002 substance use, 219 three matrices, comparison of results, 1003 THC recovery, 1009 Parental influence, on adolescent cannabis two matrices, comparison of results, 1003 THC stability, 1009 On-site drug testing, 999 Oral mucosal disease, e73 use, 216–217 alere DDS V Test, 1001 Oral tongue cancers, e97 future directions in, 220 detection limit, 1000 marijuana use and, e97 Parental monitoring, 972 matrix of choice, 999–1000 Orchialgia, chronic, 446 Parental warmth on-site oral fluid testing, 1002 Orexigenic effect, 644 and monitoring, 218 on-site urine testing, 1001 Orexin system, 534 and parenting style, 219 use of addictive properties of drugs abuse, role Parenting style, 219 Parkinson’s disease (PD), 792, 805, 918, 963 emergency department, 1003 in, 535 cannabinoids, effect of, 919 forensic autopsies, 1002–1004 cannabinoid dependence, role in, 538 characteristic primary health care, 1004 potential therapeutic utility, 536 schools, 1003 ORG27569 allosteric modulators, 575 bradykinesia, 918 Opiates/opioids, 182, 665 binding site, elucidation of, 578 postural instability, 918 animal exposure in vivo studies, 578 rigidity, 918 effects of CBD, 942 ORG27759 allosteric modulators, 575 tremor, 918 drug-related death, 941 ORG29647 allosteric modulators, 575 endocannabinoid system, 918 Opiates use disorder Organon compounds, 575 6-hydroxydopamine model, 920 treatment strategy ORG27569, 575 l-dopa treatment, 918 methadone use, 940 ORG27759, 575 1-methyl-4-phenyl-1, 2, 3, µ−Opioid receptors, 941 ORG29647, 575 Opioids, 452 Oromucosal spray administration, 895 6-tetrahydropyridine model, 920 Opioid withdrawal symptoms Oropharyngeal cancers, e97 primate models, 921 THC, effect of, 874 Orthosteric ligands, 574 rotenone model, 920 Oppositional defiant disorder, e66 Otenabant, 653 Past month cannabis use Oral allergy syndrome (OAS), 519 development program, 653 by age group and country, 37 Oral fluid (OF), 1008 Overweight, 650 by age group, Europe and the United analysis Oxidative stress, 780, 831 gas chromatography–mass spectrometry beta cells dysfunction, 781 States, 40 Oxytocin, 1071 Past year cannabis use (GC/MS), 1010 immunoassay screening, 1010 P by age group, Europe, Canada, and the liquid chromatography with United States, 39 PAG. See Periaqueductal gray matter (PAG) tandem mass spectrometry PAHs. See Polycyclic aromatic hydrocarbons Pathogenesis, 467 (LC-MS/MS), 1010 Patient flow time of flight (TOF) detection, 1010 (PAHs) collection device, 1008–1009 Pain control through the study, e198 cannabinoid recovery, 1011 Pavlovian conditioning, 318 desirable characteristic, 1008 endogenous cannabinoids, role of, 909 PBC. See Primary biliary cirrhosis (PBC) collection pad, 1009 opioids, role of, 909 PBE. See Poisson–Boltzmann equation (PBE) transportation buffer, 1009 Pain Disability Index (PDI), e162 PCE. See Prenatal cannabis exposure (PCE) THC recovery, 1009 Painful neuropathy, 912 PCU. See Problematic cannabis user (PCU) composition, 1008 Pain management, 824, 864 PD. See Parkinson’s disease (PD) cholesterol, 1008 cannabinoids, use of, 864 PDI. See Pain Disability Index (PDI) electrolyte, 1008 pharmocotherapy class pDomTHREADER, 683 enzyme, 1008 PEA. See Palmitoylethanolamide (PEA) epithelial cell, 1008 dorsal horn inhibitory mechanism, 908 Pedicularis densiflora, 840 mucin, 1008 membrane stabilizing agents, 908 Peer influence, nature of, 189–190 protein, 1008 Palliative cancer, symptoms relief Peers vs. friends, 189 vitamin, 1008 approved cannabinoid, 862 Pelvic viscera, sensory innervation, 440 water, 1008 Palmitoylethanolamide (PEA), 675 Pentylenetetrazole (PTZ) model, 797 disposition of cannabinoid, 1010–1013 N-Palmitoylethanolamine, 626, 951 Pepcan-12, 579 marijuana smoking, 1011 Pancreas, 444, 780 Pep pills, e152 oral administration, 1013 Pancreatic polypeptide (PP), 780 Peptide YY(PYY), 780 smoking and oral administration, 1013 Panic attack-like behaviors, e142 Perceived behavioral control, 218–220 drug stability, 1008–1009 PANSS. See Positive and negative syndrome Percentage marijuana recovery, 1008–1009 scale (PANSS) of current age cohorts and corresponding Papyrus, 112 age of first use for cannabis, 37 Paralytic ileus of past year cannabis use by age group and country, 36 Perception of drugs, 201

1138 Index Periaqueductal gray matter (PAG), e141 Polyketide synthases (PKSs), 15 Pretreatment dropout, 1026 Perinatal exposure, 741 Polysubstance dependence, 1058 Prevalence of dual pathology, in cannabis Periodontal disease, e77 Polysubstance use, 75 Peripheral signals, 640 POMC. See Proopiomelanocortin (POMC) addicts in treatment, 67 Peripheral vascular disease, 483 Popular media, e154 age for cannabis use vs. mental Peroxisome proliferator-activated receptor POSIT. See Problem-oriented screening disorders, 68 (PPAR) instrument for teenagers (POSIT) current diagnoses of axis I disorders alpha agonist, 744 Positive and negative syndrome scale Peroxisome proliferator-activated receptor-γ assessed by the MINI, 67 (PANSS), 29, 792, 1088 distribution of lifetime comorbid mental (PPARγ), 406, 805, 960 Positive well-being Personality disorders, 66 disorders, 67 Personalized medicine, 590 cannabis, 309–310 distribution of personality disorders in Pertussis toxin (PTX), 566, 732 future directions, 313 PET. See Positron emission tomography (PET) limitations, 313 patients with lifetime cannabis PGE2. See Prostaglandin E2 (PGE2) misuse, 67 Pharmacokinetic activity, 162 component Madrid study on, 67 Pharmacokinetic (PK) models, 387 happiness, 309, 310 Primary biliary cirrhosis (PBC), 587 Pharmacological studies life satisfaction, 309, 310 Primary dystonias, 833 Problematic cannabis user (PCU), 974 in rats, e105 Positron emission tomography (PET), 293, negative variables, with Pharmacology, 822 375, 789, 918 multivariate multinomial logistic Pharmacotherapy trial, 1032 regression, 977 Phencyclidine, 665 Posterior cingulate cortex (PCC), e55 variables positive, with Phenobarbital, 665 Postnatal day (PND), 634 multivariate multinomial logistic Phenothiazines, 456 Postoperative pain, 453 regression, 978 Phentermine, 650 Problematic use of cannabis (PUC), e181 Phenylacetylindoles, 692, 721 multidimensional model for Problematic use of marijuana (PUM), e181 Phosphatidylinositide-3-kinases (PI3K), pathophysiology, 452 Problem behavior theory (PBT), e19 Problem-oriented screening instrument for 560, 566 Postsynaptic density protein 95 (PSD-95), 734 teenagers (POSIT), 973 Phospholipase C, 631 Posttraumatic stress disorder (PTSD), e132, 872 Processing speed, e67, 74, 262 Phosphorylation, 566 Proconvulsant effects, 434 marijuana, effect of, 872 of cannabis, 434 of ERK by CB1, 566 nightmares, 825 medically administered CBD, 434 Phytocannabinoids, 14, 555, 607, 609, 654, Potassium channels, 567 Prodromal nausea, 467 Potency, 25, 26 Progesterone, 672 706, 749 PP. See Pancreatic polypeptide (PP) Program agenda for the drug court chemical structures, 555 PPAR. See Peroxisome proliferator-activated model, 194 effects, 609 Proinflammatory cytokines, 559 intraocular pressure, effect on, 750 receptor (PPAR) Proliferator-activated receptors (PPARs), 744 PPARα receptors, 473 Proopiomelanocortin (POMC), 640 cat, 750 PPARγ. See Peroxisome proliferator-activated Propyl cannabinoids, 21 dog, 751 Prostacyclin, 731 human, 749 receptor-γ (PPARγ) Prostaglandin biosynthesis monkey, 751 Preclinical studies, 773 cannabigerol, role of, 963 rabbit, 750 Preclinical work, 775 Prostaglandin E2 (PGE2), 724, 730, 796 rat, 751 Prefrontal cortex (PFC), e54, 71, 152 Prostaglandin production pathway PI3K. See Phosphatidylinositol-3-kinase Pregabalin, e161 CBG, effect of, 960 Pregnancy, 162, 531 Prostaglandins, 731 (PI3K) Prostate carcinoma, 866 Pilocarpine and pentylenetetrazol (PTZ), 608 characteristics of women, using cannabis pathogenesis, 866 Pittsburgh Sleep Quality Index (PSQI), e163 during, 162 Prostatectomy, 455 PKC. See Protein kinase C (PKC) Prostatic serum antigen (PSA), 866 PK models. See Pharmacokinetic (PK) models Prelimbic frontal cortex (PL), e135 Protein folding, 829 PL. See Prelimbic frontal cortex (PL) Premammillary hypothalamic nucleus, e143 Protein kinase A (PKA), e104 Placebo, 824 Premorbid IQ, and cannabis Protein kinase C (PKC), e104, 534 Plasma cells, 518 Protein–protein docking, 685 Pleasure pathway, 319 findings from longitudinal studies, 229 Proteome, e3 P42/44 MAP kinase, 756 possible explanation of link to cannabis Proton magnetic resonance spectroscopy PND. See Postnatal day (PND) (1H-MRS), 350 Pneumomediastinum, 501 use, and psychosis, 230 Prunus persica, 519 Pneumothorax, 501 Premorbid neuropsychological abilities, 224 PSD-95. See Postsynaptic density protein 95 POC. See Point-of-collection (POC) Prenatal cannabis exposure (PCE), 161 (PSD-95) Point-of-collection (POC), 999 PSQI. See Pittsburgh Sleep Quality Index Poisson–Boltzmann equation (PBE), 686 detection methods and accuracy of (PSQI) Poisson regression analysis, e3 prevalence estimates, 162 Psychiatric comorbidity, 75, 133 Polycyclic aromatic hydrocarbons Psychiatric treatment effects on offspring, 163–166 level, CapOpus, effects of, 1090 (PAHs), 498 Bayley scales of infant development, 165 Psychoactive drugs, e151 Polydipsia, 467 behavioral alterations in children Polydrug, 162, 203 prenatally exposed to cannabis, 167 cardiovascular changes associated problems associated with, 175–176 with, 163 Polyketide pathway, 15 gestation and infant mortality, 165 neurocognitive development, 166 size effects associated with, 164 neuroimaging studies, 165 prevalence and behavioral patterns across pregnancy, 161 SAMHSA report, 161 Stanford-Binet Intelligence Scale, 165

Index 1139 Psychoactive substances, 41 Rapid eye movement (REM), 878 Rodents, e142, 741 Psychological and relational problems, Rave culture, e15 behavior, e142 experienced by substance users, 183 ecstasy, e15–e16 Romberg’s test, 851 Psychological effects ideology of PLUR, e15 Root mean square deviation (RMSD), 687 RCT. See Randomized clinical trials (RCT) Root mean square fluctuation (RMSF), 687 of acute cannabis intoxication, 81 RCVS. See Reversible vasoconstriction ROS. See Reactive oxygen species (ROS) present in drug addicts, 183 RP. See Relapse prevention (RP) Psychopathological symptoms, 48 syndrome (RCVS) RPE. See Retinal pigmented epithelium (RPE) Psychopharmacological effects, 54 Reaction time (RT), 381 RT. See Reaction time (RT) Psychosis, 25, 29, 80, 414, 873 Reactive oxygen species (ROS), 677, 803 RXR. See Retinoid X receptor (RXR) cannabis use, effect of, 283 Recency of parents’ cannabis use and dopamine release S children’s initiation, 217 stress-induced, 281–282 Recent-onset schizophrenia (ROS), e55 SAD. See Social anxiety disorder (SAD) ECS, effect on, 283 Receptor–agonist interactions, 718 Saliva, biochemical composition, 1008 gene–environment interaction, 282 Receptor trafficking, 734 Salting out technique (SALLE), 991 inducing effects of cannabis, 30 Recreational drug SAMHSA. See Substance Abuse and Mental self-medication by marijuana, 872 Psychosocial derailment, and problem online available, 844 Health Services Administration Recreational drugs, 162 (SAMHSA) accumulation, 146 Recreational use, cannabis, future research Sativex, 943, 1010, 1071 Psychosocial stress, 281. See also Psychosis oromucosal spray Psychostimulants, 535, 665 directions, 314 spasticity, treatment, 959 Psychotic disorder, e30 Reference spectrum, 985 Sativex compound, 895 Register of Australian Drug and Alcohol SBIRT. See Screening, brief intervention, and marijuana, effect of, 873 referral to treatment (SBIRT) Psychotic illness, 47, 48 Research (RADAR), 1078 SC. See Synthetic cannabinoids (SC) Psychotic patients, 49 Relapse prevention (RP), e194, 1057, 1061 SCBs. See Synthetic cannabinoids (SCBs) Psychotic spectrum disorder, 281 Schedules for, clinical assessment in Psychotic symptoms, 66, 415 strategies, 1062 neuropsychiatry (SCAN) Psychotomimetic effects, 49 cannabis craving, understanding of, 1062 interview, 1087 Psychotropic effects, 414 cognitive distortion, 1062 Schizophrenia, 47, 66, 80, 224, 336, 346, 358, PTSD. See Posttraumatic stress disorder cognitive skill acquiring, 1062 414, 788, 1087 emotion, 1062 attribution style, 358 (PTSD) psychoeducation, 1062 candidate genes, 336 PTX. See Pertussis toxin (PTX) role play, 1062 and cannabis, 337 PTZ. See Pilocarpine and pentylenetetrazol cognition, 358 REM. See Rapid eye movement (REM) deficits in social knowledge, 358 (PTZ) Resin (hash), 25 diagnoses, 336 PUC. See Problematic use of cannabis (PUC) Resin-type cannabis, e3 disorders, 361 Pulsatility indices, 163 Resistance indices, 163 emotion recognition, 358 PUM. See Problematic use of marijuana Response inhibition, e67 functional imaging studies, 361 Restriction fragment polymorphisms gene–cannabis interactions, 337 (PUM) catechol-O-methyltransferase, 337 Purkinje cell excitability, 408 (RFLP), 7 neuregulin 1, 338 PyMOL molecular graphics system, 686 Retinal ganglion cell (RGC), 761 gene–environment interactions, 336 Pyrazolopyridines, 602 Retinal pigmented epithelium (RPE), 763 heritability for, 80 Pyrazolylidene, 600 Retinoid X receptor (RXR), 672 marijuana, effect of, 873 Pyridine, 598 Reversible cerebral cannabis arteriopathy, 490 negative symptoms, 788 Pyrimidine, 598 Reversible vasoconstriction syndrome anhedonia, 788 PYY. See Peptide YY(PYY) apathy, 788 (RCVS), 487 social withdrawal, 788 Q Reviews and metaanalyses on cannabis neurofunctional Alterations, 360 and nonaffective psychosis, 46 QLIP. See Quality of Lfe Impairment by Pain and cognition, 225 patients, 46 (QLIP) Reynaud phenomena, 483 prevalence, 336 RGC. See Retinal ganglion cell (RGC) rates of, 80 Qsymia, 650 Rhesus monkeys, 697 related disorder Quality of Lfe Impairment by Pain (QLIP), Rho-GTPase signaling pathways, 565 amphetamine-induced DA release, 282 Right censoring, 139 spectrum psychosis, 1087 e162 Right inferior frontal gyrus (RIFG), 274 symptoms, 336 QUARK algorithm, 684 Rimonabant, 473, 651, 697, 920, 964 anhedonia, 336 Quetiapine, 943, 1032 cognitive, 336 Quinolones, 602 antihypokinetic activity, 920 impairment of sensorimotor gating, 336 glutamate release, effect on, 920 social withdrawal, 336 R Risk and protection factors influencing theory of mind, 358 Schizophreniform psychosis, 414 RADAR. See Register of Australian Drug and substance use, 203 School-based drug prevention program, 201 Alcohol Research (RADAR) Risperidone, 887 RMSD. See Root mean square deviation Radial diffusivity (RD), 348, 393 Radioimmunoassay, 48 (RMSD) Random amplified polymorphic DNA RMSF. See Root mean square fluctuation (RAPD), 7 (RMSF) Randomized clinical trials (RCT), e161 Roadside Testing Assessment project, 1000 Randomized controlled clinical trials, e164 Road traffic accident Randomized controlled trials, 434 cause, driving under the influence (DUI) of drugs, 849 Robetta’s algorithm, 684

1140 Index SNPSTR database, e7–e8 SNr. See Substantia nigra pars reticulata School-oriented programs, 202 Shisha, 115 SCN1A gene mutation, 434 Short Form 36 Health Survey (SF-36), e163 (SNr) Screening, brief intervention, and referral to Short inflammatory bowel disease Social anxiety disorder (SAD), e134, 872 Social cognition, 46 treatment (SBIRT), 1102 questionnaire (SIBDQ) Social development model, 292 Screening instruments score, 918 Social drug, 189, 194 Short inventory of problems-alcohol and Social hypothesis, 368 characteristics, e171–e181 drugs (SIP-AD), e181 Social network during adolescence, 192 process of selection and analysis, e171 SIBDQ score. See Short inflammatory Social phobia, 434 Screening tests, by immunoassay, 239 bowel disease questionnaire SOD. See Superoxide dismutase (SOD) SDS-PAGE analysis, 15 (SIBDQ) score Sources of information on illicit drugs, Seized material analysis, GC-MS, use of, 985 Siblings, 46, 49 Selective serotonin and norepinephrine SIDS. See Sudden infant death syndrome reported by European young (SIDS) people, 202 reuptake inhibitor (SSNRI), e161 Signaling pathways, 577 Specialized addiction treatment, 1027 Selective serotonin reuptake inhibitors Simulation of the public speaking test SPECT. See Single photon emission computed (SPST), e134 tomography (SPECT) (SSRIs), e161, 490, 885 Single nucleotide polymorphism (SNP) Spice, 840, 849, 986 Self-help for alcohol and other drug use and assay, e4 diamond, 986 Single nucleotide polymorphism database neurologic effects, 844 depression (SHADE), e207 (DBSNP), 586 psychoactive component Self-medication, 303 Single nucleotide polymorphisms (SNPs), identification, 841 336, 340, 585 sympathomimetic effects, 844 hypothesis, 415, 424 nonsynonymous, 586 variant theory, 312 Single photon emission computed spice diamond, 840, 841 Self-report tomography (SPECT), spice gold, 841 of adult population e134, 940 Sprague Dawley rats, 653, 660 Sinsemilla (skunk), 25, 29, 418 SPST. See Simulation of the public speaking cannabis use prevalence, e187 SIP-AD. See Short inventory of problems— test (SPST) and biological measurements alcohol and drugs (SIP-AD) SPT. See Skin prick tests (SPT) Skills, 49 SR141716A concordance between, e186 based programs, 201, 202 rapid eye movement (REM), effect concordance with Skin, 544 on, 878 Skin lesions, 546 slow wave sleep (SWS), effect armed forces, e190 Skin prick tests (SPT), 522 on, 878 driving population, e189 Sleep disorders, 872–873 wakefulness induction, role drug users in treatment, e190 marijuana, use of, 872 in, 878 emergency department patients, e190 THC, effect of, 865 Src activation pathways, 580 HIV-infected youth, e190 Sleep latency, acute administration of SSNRI. See Selective serotonin and pregnant women, e190 marijuana, effect of, 872 norepinephrine reuptake inhibitor university students, e189 Sleep, physiological role of (SSNRI) Self-validation, 310 endocannabinoid, 878 SSRIs. See Selective serotonin reuptake Sensation seeker, 56 Sleep-wake cycle, 535 inhibitors (SSRIs) Sensorimotor gating, 337 cannabis, effect of, 878 Stabilization energy (∆Eiso), e124 deficits, 338 SLF. See Superior longitudinal Staphylococcus aureus, 965 Serotonergic neuronal system, 329 fasciculus (SLF) Steatosis, 587 Serotonergic systems, 329 Slow transit constipation Stilbene synthase (STS), 15 Serotonin1A, 705 cannabinoid, effect of, 955 Stimulants, e152 Serotoninergic agents, 721 Slow wave sleep (SWS), 878 abuse and dependence treatment SERS. See Surface enhanced Raman Smokers, effects of CBD, 943 dopamine uptake blockers and releasers, Smoking inhibition use of, 941 spectroscopy (SERS) CBD inhaler, use of, 942 abuse potential, 941 Set-shifting, 46 CBD, use of amphetamine, 940 Sexual mechanism of action animal exposure CB1 receptor antagonist, 942 effects of CBD, 942 attitudes, 182 FAAH inhibition, 942 cocaine, 940 behavior, 181, 182 use of low dose CBD, 942 dependence Smoking, lead to increased total exposure of pharmacotherapies, development effect of drugs on, 183 THC, 30 of, 941 desire, 182 Smoking, synthetic cannabinoids, 445 dopamine level, increase in, 941 difficulties, 184 Smuggling, 122 euphoria, 941 disorders, 181 SNc. See Substantia nigra pars compacta methamphetamine, 940 excitement, 182 (SNc) Stimulus–response (S-R) association, 268 expectations, 185 SNpr. See Substantia nigra pars reticulata STN. See Subthalamic nucleus (STN) function, 182 (SNpr) Street drug, 869 performance, 182, 183 SNPs. See Single nucleotide polymorphisms Streptozotocin (STZ), 780 pleasure, 183 (SNPs) satisfaction, 181 violence, 182 Sexually transmitted diseases, 183 SF-36. See Short Form 36 Health Survey (SF-36) SF-36 health survey results, 934 SHADE. See Self-help for alcohol and other drug use and depression (SHADE) Shapiro Tourette syndrome severity scale (STSSS), 888

Index 1141 Stress, 62 Superoxide dismutase (SOD), 782 JWH-019, 984 brain response, 280 Surface enhanced Raman spectroscopy JWH-073, 984 DA-related mental illnesses, 279 JWH-122, 984 drugs use disorders, 279 (SERS), 1022 separation of, 984 evaluation, 280 Survey of young people in Egypt (SYPE), 114 K2, 849 induction, 280 Swallowers, 123 legal responses to, 56 and mental disorder, 279–280 SWS. See Slow wave sleep (SWS) legislation, 854 neuropsychiatric disorder, 279 Sympathetic nervous system (SNS), 279 metabolite, 985 schizophrenia, 279 Synaptic plasticity, 633 nonclassical, 752 psychosis illnesses, 280 Synaptic potentiation, 635 abnormal cannabidiol, 752 related HPA activity, 279 Synaptic stripping, 402 profile of users, 57 study, 280 Synopsis of C. sativa sectional species, psychoactive effect animal models, 280 calmness, 842 subspecies, and varieties, 6 euphoria, 842 Stressful interviewing protocol, 280 Synthetic analogs, 593 relaxation, 842 Striatal damage Synthetic cannabinoids (SCBs), 54, e151, 173, reasons for usage, 54–56 receptor agonist, 982 3-nitropropionic acid-induced, 924–926 607, 632, 692, 751, 982 recreational use, 986 quinolinic acid-induced, 926 aminoalkylindoles, 752, 982 replacement user, 58 research chemicals, 985, 988 in vitro study, 926 WIN55212-2, 752 seized product, 988 STR locus, e7 behavioral effects, 693 serum or blood analysis Stroke, 489 quantitative method, 989 anxiety, 692 spice, 849 onset, 489 confusion, 692 structure, 983 Structural implications, cannabis use of, psychosis, 692 summary of the four profiles, 56 speech, 692 5th generation 153–155 blood concentration in suspected driver, APINACA, 982 gray matter, 153 5F-PB-22, 982 moderating factors, 155 851–852 UR-144, 982 potential confounding, 155 brand names, 55 timeline of major legal and media events in white matter, 154 cannabis-like effects, 849 STSSS. See Shapiro Tourette syndrome classical, 751 the United States, 56 tolerance, 853 severity scale (STSSS) BW146Y, 751 urine analysis STZ. See Streptozotocin (STZ) HU-211, 751 Subcortical dementias, 833 nabilone, 751 quantitative method, 992 Subjective effects, 823 clinical consequence, 842–844 users, types, 54 Subjective norms, 218 clinical effects, 692 Synthetic cathinones, e105, e151 Substance Abuse and Mental Health hypertension, 692 Synthetic Drug Abuse Prevention Act hyperventilation, 692 Services Administration mydriasis, 692 (2012), e153 (SAMHSA), 1051, 1078 nausea, 692 guideline, 985 reddened conjunctivae, 692 T Substance abuse and mental health services vomiting, 692 administration (SAMHSA), e187 clinical presentation, of intoxication, 850 Tail-flick assay, 445 Substance abuse prevention, 1078 concentration in biological media, 984 TAs. See Traffic accidents (TAs) Substance-related problem, 317 consumption effect, typical performance TAU. See Treatment as usual (TAU) Substance use Tau hyperphosphorylation, 830 controlled, e169 deficit, 849 Tauopathy, 831 harmful, e169 demographics associated with, 57 Tautomerization, 676 nonproblematic, e169 detection, analytical challenge, 853 TCAs. See Tricyclic antidepressants (TCAs) problematic, e169 discriminative stimulus effects, 696 T2D. See Type 2 diabetes (T2D) risky, e169 TEAC. See Trolox equivalent antioxidant Substance use disorder (SUD), 62, 873–874, cross-tolerance, 697 e169, e170, 972, 1057, 1059, 1087 tolerance, 697 capacity (TEAC) cognitive behavioral therapy, use of, 1058 driving skills, effect on, 853 Telescoping effect, 132 marijuana, role of, 873 drug aficionado, 59 Temporal perception, 185 role of early CU in CUD risk in context drug testing, 845 Tenax collection method, 1019 of, 143 immunoassays, 845 Terpenophenolic, 3 self-monitoring, 1103 liquid chromatography-mass Substance use intervention, 1102 constituents, 14 Substance use problem, 1026 spectrometry, 845 Tesofensine, 650 Substance use treatment, 1028 standard urine drug testing Testicular germ cell tumors Substantial problem, e154 Substantia nigra pars compacta (SNc), 918 procedures, 845 logistic regression model, e97 Substantia nigra pars reticulata (SNpr), effects, 611 marijuana use and, e97 e144, 918 multivariate adjustment, e97 Subthalamic nucleus (STN), 918 of legislation, 841–842 nonseminoma, e97 Sudden infant death syndrome (SIDS), 530 safe driving, interfere with, 851 pure seminoma, e97 Sulfamoyl benzamides, 598 experimental user, 58 Test of memory malingering, 295 Suncus murinus, 953 frequently detected Testosterone, 182 Superior longitudinal fasciculus (SLF), 347 AM-2201, 850 lowering medicaments (TLM), 965 JWH-018, 850 habitual user, 59 herbal smoking blend, use as, 985 isobaric compound JWH-015, 984

1142 Index Tetrahydrocannabinol (THC), e189, 299, Thyroid-stimulating hormone (TSH), 462 TSGS. See Tourette syndrome global 321, 415, 593, 763, 959, 1008, 1018, Thyroxin-binding-globulin (TGB), 463 scale (TSGS 1019, 1021, 1031, 1068, 1087. See also TIA. See Transient ischemic attack (TIA) ∆9-Tetrahydrocannabinol (THC) Tiagabine, 775 TSH. See Thyroid-stimulating hormone (TSH) Timeline follow-back (TLFB), 1088 TSLP. See Thymic stromal lymphopoietin anxiety-like symptom, 304 Titration of THC intake during smoking, 26 awakenings, effect on, 879 TLESRs. See Transient lower esophageal (TSLP) bicyclic analogs, 593 TTI. See Theory of triadic influence (TTI) changes in concentrations in blood sphincter relaxations (TLESRs) Tumor necrosis factor (TNF), 796 TLFB. See Timeline follow-back (TLFB) Tumor-promoting effects, 500 samples, 27 TLP. See Thaumatin-like proteins (TLP) Two-option experimental task, 293 chemical structures, 841 TLR4-dependent pathway, 473 concentrations in biological samples, 27 TM. See Trabecular meshwork (TM) nonwork option, 293 content in different plants varies according TNF. See Tumor necrosis factor (TNF) work option, 293 Tobacco, 80 Type 2 diabetes (T2D), 673 to a number of factors, 25 TZDs. See Thiazolidinediones (TZDs) detection, gas chromatographic-mass cigarette smoking, 495 TOC. See α-Tocopherol (TOC) U spectrometric method, use of, 1019 α-Tocopherol (TOC), e127 drowsiness, effect on, 879 Toll-like receptors (TLR), 403 UC. See Ulcerative colitis (UC) ocular delivery, 763 Tourette’s syndrome clinical global Ulcerative colitis (UC), 475, 932, 954 Unambiguous structure elucidation challenges, 763 impression scale (GTS-CGI), 888 positive driver, 850 Tourette syndrome, 833 NMR, use of, 985 psychomimetic effect, 281 Tourette syndrome global scale (TSGS), 887 United Nations Office on Drugs and Crime sleep efficiency, effect on, 879 Tourette syndrome symptom list (TSSL), 888 sleep latency, effect on, 879 Towards No Drug Abuse (TND), 1081, 1082 (UNODC), 90, 107, 870, 982 sleep-wake cycle, effect on, 879 Trabecular meshwork (TM), 749 United States standard substance, 1019 Traffic accidents (TAs), 235 treatment past month cannabis use by age group, 40 Global Status Report on Road Safety, past year cannabis use by age group, 39 vs. placebo report, 235 percentage of older adults using cannabis STSSS score, changes in, 889 TS-CGI score, changes in, 890 risk factors, 235 in past year, 41 YGTSS score, changes in, 889 and synthetic cannabinoid, 852–853 United States Drug Enforcement Agency, 123 vehicular risk factors, 235 United States Food and Drug Administration tricyclic analogs, 593 Trail making test, 1088 ∆9-Tetrahydrocannabinol (∆9-THC), e127, Transcranial magnetic brain stimulation, 374 (FDA), e160 Transcription factor, 538 Univariate logistic regression model, 975 e132, e141 Transcriptomes, e5 Tetrahydrocannabinolic acid (THCA), e2, 7 Transient ischemic attack (TIA), 486, 487 covariate Tetrahydrocannabinolic acid synthase Transient lower esophageal sphincter family/friendly/scholastic environments, 977 (THCAS), 15, 19 relaxations (TLESRs), 953 lifestyle and use of leisure time, 977 Tetrahydrocannabivarian (THC-V), 21, 104 Transient receptor potential cation channel self-opinion, 977 Tetrahydrocannabivarinic acid (THCVA), 21 Tetramethylcyclopropy, 598 (TRP), 406 UNODC. See United Nations Office on Drug TGB. See Thyroxin-binding-globulin (TGB) Transient receptor potential cation channel and Crime (UNODC) Thaumatin-like proteins (TLP), 521 THC. See ∆9-tetrahydrocannabinol (THC); ubfamily V member 1 (TRPV1), e141 Unprovoked seizure, 433 Transient receptor potential (TRP) Urinalysis assessments, e154 ∆9-tetrahydro-cannabinol (THC) Urinalysis testing, e151 THCA synthase (THCAS), e2, e4, e5 channels, e137 Urine drug screening (UDS), 162 Transient receptor potential vanilloid type-1 Urine sample analysis activity, e6 THC carboxylic acid (THCCOOH), 1019, (TRPV1) channels, 607, 612, 632 enzyme-linked immunosorbent assays Transmembrane domains (TMs), 558 (ELISA), use of, 988 1021, 1022 Transporter inhibitors, 755 THC/CBD ratio, 25, 26 Treatment as usual (TAU), 1087, 1088 homogeneous enzyme immunoassay THC/CBD ratios, e58 Treatment attrition, 1095 (HEIA), use of, 988 THCCOOH. See THC carboxylic acid Treatment facility, contact with, 1089 T regulatory cells, 509 Users of new psychoactive substances (TH-COOH) Triaryl derivatives, 600 rates of cannabis use in, 175 THC-COOH. See 11-nor-9-carboxy- Triazolam, 771 Trichomes, 3 US National Survey on Drug Use and Health delta 9-tetrahydrocannabinol Tricyclic antidepressants (TCAs), e161 (NSDUH) data, 39 (THC-COOH) Tricyclic cores, 602 Theories and empirical support, e20 Trolox equivalent antioxidant capacity V Theories of synergism, 455 Theory of planned behavior, 218 (TEAC), e127 Vagal nodose ganglia, 644 Theory of triadic influence (TTI), 1037 TRP. See Transient receptor potential cation Vagotomy, 643 Therapeutic alliance domain, e206 Vagus nerve, 644 Therapeutic Goods Administration channel (TRP) (TGA), 106 TRPV1 role in ghrelin actions, 644 Thiazolidinediones (TZDs), 673 TRPV1 channels. See Transient receptor Valine (Val) allele, 418 Thiazolylidene, 600 Val66Met BDNF gene polymorphism, 717 Thromboxane, 512, 731 potential vanilloid type-1 (TRPV1) Vanilloid-1 receptor (TRPV1), 878 Thymic stromal lymphopoietin (TSLP), 546 channels VAS. See Visual Analog Scale (VAS) Thyroid function tests, 463 Vascular imaging, 490 Vasoconstriction effect, 483 Venlafaxine, 943, 1033, 1071 Ventral tegmental area (VTA), 534 Ventricular alterations, e54

Index 1143 Verbal learning, 74 WAT. See White adipose tissue (WAT) Y VGCCs. See Voltage-gated calcium channels Weight-loss drugs, 650 White adipose tissue (WAT), 651 Yale global tic severity scale (YGTSS), 888 (VGCCs) White House Office of National Drug Control Y chromosome, e4 Videobronchoscopy, 498 Years lived with disability (YLDs), 90 Visceral cancer pain, 441 Policy, 869 Years lost due to premature mortality Visceral hypersensitivity, 441 White matter, 154 Visceral pain, 441 WHO. See World Health Organization (YLLs), 90 YGTSS. See Yale global tic severity scale anatomic and functional features of, 442 (WHO) cannabinoids, 441 WIN55, 212-2 (YGTSS) Visual acuity, 122 YMRS. See Young mania rating scale (YMRS) Visual analog scale (VAS), 773 induced gastric emptying delay, 951 Young age at CU onset and its association Visual reaction time, 71 neuroprotective effect, 920 Visuomotor tracking, 373 repeated administration in rat, effect of, 951 with CUD risk, 139 Visuospatial memory, 152 in vivo effect in rat, 950 empirical evidence, 139 Voltage-gated calcium channels Wisconsin Card Sorting Test (WCST), e54 epidemiological studies on earlier onset of Wistar audiogenic rats (WAR), 608 (VGCCs), 1033 Wistar rats, e145, 666 CU in CUD risk, 141 Voxel-based morphometry (VBM), e55 Withdrawal symptom important methodological aspects VTA. See Ventral tegmental area (VTA) newly abstinent drug user, 321 Vulnerability WM. See Working memory of studies on early onset of substance use Working memory, 46, 47, 49, e67, 71, and substance use disorder risk, 143 general heritable, for disinhibitory behavior and psychopathology, 146 155–157 methodological considerations, 139 World Health Organization (WHO), 92, 113, possible explanations as a phase of vulnerability for addiction, in adolescence, 143 e171, 860, 1008 for association between a younger age at traffic accidents estimate, 235 first CU and CUD risk, 140 for THC effects in adolescence, 144 X Young mania rating scale (YMRS), 792 W Youth cultures, e12 X chromosome, e4 Youth interventions foundation, 1051 Walk-and-turn (WAT) test, 851 Xerostomia, e73 WAR. See Wistar audiogenic rats (WAR) X-ray structure, of active center THCAS, 21 Z Warrant treatment, 1027 ZNF804A gene, 347 Zolpidem, 1032 Zornia latifolia, 840

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