Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature

Abstract

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis, current knowledge about the efficacy and safety of cannabis-based medicine in psychiatry is still extremely limited. So far, no cannabis-based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder.

Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress.

Practically, cannabis-based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1–2.5 mg THC/day), and the dose should be up-titrated slowly (by 1–2.5 mg every 3–5 days). The average daily dose is 10–20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day.

Keywords

cannabis-based medicine - cannabinoids - psychiatry - THC - CBD

Publication History

Received: 17 September 2023

Accepted: 17 January 2024

Article published online:
01 March 2024

• References

• 1 Ärzteblatt DÄG Redaktion Deutsches. Begleiterhebung zu medizinischem Cannabis: Bedingt aussagekräftig. Deutsches Ärzteblatt 2022 https://www.aerzteblatt.de/archiv/226212/Begleiterhebung-zu-medizinischem-Cannabis-Bedingt-aussagekraeftig Stand: 26.05.2023
• 2 Black N, Stockings E, Campbell G. et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis. Lancet Psychiatry 2019; 6: 995-1010 DOI: 10.1016/S2215-0366(19)30401-8.
• 3 Sarris J, Sinclair J, Karamacoska D. et al. Medicinal cannabis for psychiatric disorders: A clinically-focused systematic review. BMC Psychiatry 2020; 20: 24 DOI: 10.1186/s12888-019-2409-8.
• 4 McKee KA, Hmidan A, Crocker CE. et al. Potential therapeutic benefits of cannabinoid products in adult psychiatric disorders: A systematic review and meta-analysis of randomised controlled trials. J Psychiatr Res 2021; 140: 267-281 DOI: 10.1016/j.jpsychires.2021.05.044.
• 5 Lim K, See YM, Lee J. A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin Psychopharmacol Neurosci 2017; 15: 301-312 DOI: 10.9758/cpn.2017.15.4.301.
• 6 Hazekamp A, Ware MA, Muller-Vahl KR. et al. The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms. J Psychoactive Drugs 2013; 45: 199-210
• 7 Lintzeris N, Mills L, Abelev SV. et al. Medical cannabis use in Australia: Consumer experiences from the online cannabis as medicine survey 2020 (CAMS-20). Harm Reduction Journal 2022; 19: 88 DOI: 10.1186/s12954-022-00666-w.
• 8 Kimless D, Caloura M, Markos V. et al. An observational cross-sectional survey exploring the indications for and responses to medical marijuana use in certified patients in Pennsylvania. J Prim Care Community Health 2022; 13 21501319221129734 DOI: 10.1177/21501319221129734.
• 9 Lintzeris N, Driels J, Elias N. et al. Medicinal cannabis in Australia, 2016: the Cannabis as Medicine Survey (CAMS-16). Med J Aust 2018; 209: 211-216 DOI: 10.5694/mja17.01247.
• 10 Kayser RR, Raskin M, Snorrason I. et al. Cannabinoid augmentation of exposure-based psychotherapy for obsessive-compulsive disorder. J Clin Psychopharmacol 2020; 40: 207-210 DOI: 10.1097/JCP.0000000000001179.
• 11 Morena M, Berardi A, Colucci P. et al. Enhancing endocannabinoid neurotransmission augments the efficacy of extinction training and ameliorates traumatic stress-induced behavioral alterations in rats. Neuropsychopharmacology 2018; 43: 1284-1296 DOI: 10.1038/npp.2017.305.
• 12 Radwan MM, Chandra S, Gul S. et al. Cannabinoids, phenolics, terpenes and alkaloids of cannabis. Molecules 2021; 26: 2774 DOI: 10.3390/molecules26092774.
• 13 Wolfe TJ, Kruse NA, Radwan MM. et al. A study of major cannabinoids via Raman spectroscopy and density functional theory. Spectrochim Acta A Mol Biomol Spectrosc 2023; 303: 123133 DOI: 10.1016/j.saa.2023.123133.
• 14 Walsh KB, McKinney AE, Holmes AE. Minor cannabinoids: Biosynthesis, molecular pharmacology and potential therapeutic uses. Front Pharmacol 2021; 12: 777804 DOI: 10.3389/fphar.2021.777804.
• 15 Ben-Shabat S, Fride E, Sheskin T. et al. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 1998; 353: 23-31
• 16 Piomelli D, Russo EB. The Cannabis sativa versus Cannabis indica debate: An interview with Ethan Russo, MD. Cannabis Cannabinoid Res 2016; 1: 44-46 DOI: 10.1089/can.2015.29003.ebr.
• 17 Kanabus J, Bryła M, Roszko M. et al. Cannabinoids—characteristics and potential for use in food production. Molecules 2021; 26: 6723 DOI: 10.3390/molecules26216723.
• 18 de Almeida DL, Devi LA. Diversity of molecular targets and signaling pathways for CBD. Pharmacol Res Perspect 2020; 8: e00682 DOI: 10.1002/prp2.682.
• 19 An D, Peigneur S, Hendrickx LA. et al. Targeting cannabinoid receptors: Current status and prospects of natural products. Int J Mol Sci 2020; 21: 5064 DOI: 10.3390/ijms21145064.
• 20 Russo E, Guy GW. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 2006; 66: 234-246 DOI: 10.1016/j.mehy.2005.08.026.
• 21 Christensen C, Rose M, Cornett C. et al. Decoding the postulated entourage effect of medicinal cannabis: What it is and what it isn’t. Biomedicines 2023; 11: 2323 DOI: 10.3390/biomedicines11082323.
• 22 BfArM – Startseite – Abschlussbericht Begleiterhebung https://www.bfarm.de/SharedDocs/Downloads/DE/Bundesopiumstelle/Cannabis/Abschlussbericht_Begleiterhebung.html Stand: 26.05.2023
• 23 MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med 2018; 49: 12-19 DOI: 10.1016/j.ejim.2018.01.004.
• 24 MacCallum CA, Lo LA, Boivin M. "Is medical cannabis safe for my patients?“ A practical review of cannabis safety considerations. Eur J Intern Med 2021; 89: 10-18 DOI: 10.1016/j.ejim.2021.05.002.
• 25 Gottschling S, Ayonrinde O, Bhaskar A. et al. Safety considerations in cannabinoid-based medicine. Int J Gen Med 2020; 13: 1317-1333 DOI: 10.2147/IJGM.S275049.
• 26 Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis Cannabinoid Res 2017; 2: 139-154 DOI: 10.1089/can.2016.0034.
• 27 Antoniou T, Bodkin J, Ho JM-W. Drug interactions with cannabinoids. CMAJ 2020; 192: E206 DOI: 10.1503/cmaj.191097.
• 28 Arnold JC, McCartney D, Suraev A. et al. The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. Clin Transl Sci 2022; 16: 10-30 DOI: 10.1111/cts.13425.
• 29 deRoon-Cassini TA, Stollenwerk TM, Beatka M. et al. Meet your stress management professionals: The endocannabinoids. Trends Mol Med 2020; 26: 953-968 DOI: 10.1016/j.molmed.2020.07.002.
• 30 Cohen K, Weizman A, Weinstein A. Modulatory effects of cannabinoids on brain neurotransmission. Eur J Neurosci 2019; 50: 2322-2345 DOI: 10.1111/ejn.14407.
• 31 Müller-Vahl KR, Bindila L, Lutz B. et al. Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome. Neuropsychopharmacology 2020; 5: 1323-1329 DOI: 10.1038/s41386-020-0671-6.
• 32 Russo EB. Clinical endocannabinoid deficiency reconsidered: Current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis Cannabinoid Res 2016; 1: 154-165 DOI: 10.1089/can.2016.0009.
• 33 Linares IM, Zuardi AW, Pereira LC. et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry 2019; 41: 9-14 DOI: 10.1590/1516-4446-2017-0015.
• 34 Zuardi AW, Rodrigues NP, Silva AL. et al. Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol 2017; 8: 259 DOI: 10.3389/fphar.2017.00259.
• 35 Skelley JW, Deas CM, Curren Z. et al. Use of cannabidiol in anxiety and anxiety-related disorders. J Am Pharm Assoc (2003) 2020; 60: 253-261 DOI: 10.1016/j.japh.2019.11.008.
• 36 Blessing EM, Steenkamp MM, Manzanares J. et al. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 2015; 12: 825-836 DOI: 10.1007/s13311-015-0387-1.
• 37 Cairns EA, Benson MJ, Bedoya-Pérez MA. et al. Medicinal cannabis for psychiatry-related conditions: An overview of current Australian prescribing. Front Pharmacol 2023; 14: 1142680 DOI: 10.3389/fphar.2023.1142680.
• 38 Buckner JD, Schmidt NB, Lang AR. et al. Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. J Psychiatr Res 2008; 42: 230-239 DOI: 10.1016/j.jpsychires.2007.01.002.
• 39 Salazar CA, Tomko RL, Akbar SA. et al. Medical cannabis use among adults in the Southeastern United States. Cannabis 2019; 2: 53-65
• 40 Turna J, Simpson W, Patterson B. et al. Cannabis use behaviors and prevalence of anxiety and depressive symptoms in a cohort of Canadian medicinal cannabis users. J Psychiatr Res 2019; 111: 134-139 DOI: 10.1016/j.jpsychires.2019.01.024.
• 41 Bergamaschi MM, Queiroz RHC, Chagas MHN. et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology 2011; 36: 1219-1226 DOI: 10.1038/npp.2011.6.
• 42 Masataka N. Anxiolytic effects of repeated cannabidiol treatment in teenagers with social anxiety disorders. Front Psychol 2019; 10: 2466 DOI: 10.3389/fpsyg.2019.02466.
• 43 Crippa JAS, Derenusson GN, Ferrari TB. et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. J Psychopharmacol (Oxford) 2011; 25: 121-130 DOI: 10.1177/0269881110379283.
• 44 Kwee CM, Baas JM, van der Flier FE. et al. Cannabidiol enhancement of exposure therapy in treatment refractory patients with social anxiety disorder and panic disorder with agoraphobia: A randomised controlled trial. Eur Neuropsychopharmacol 2022; 59: 58-67 DOI: 10.1016/j.euroneuro.2022.04.003.
• 45 Kwee CMB, Leen NA, Van der Kamp RC. et al. Anxiolytic effects of endocannabinoid enhancing compounds: A systematic review and meta-analysis. Eur Neuropsychopharmacol 2023; 72: 79-94 DOI: 10.1016/j.euroneuro.2023.04.001.
• 46 Schmidt ME, Liebowitz MR, Stein MB. et al. The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: A double-blind, randomized, placebo-controlled proof-of-concept study. Neuropsychopharmacol 2021; 46: 1004-1010 DOI: 10.1038/s41386-020-00888-1.
• 47 Mitchell JT, Sweitzer MM, Tunno AM. et al. "I Use weed for my ADHD“: A qualitative analysis of online forum discussions on cannabis use and ADHD. PLoS ONE 2016; 11: e0156614 DOI: 10.1371/journal.pone.0156614.
• 48 Loflin M, Earleywine M, De Leo J. et al. Subtypes of attention deficit-hyperactivity disorder (ADHD) and cannabis use. Subst Use Misuse 2014; 49: 427-434 DOI: 10.3109/10826084.2013.841251.
• 49 Grotenhermen F, Müller-Vahl K. Cannabis und cannabinoide in der medizin: Fakten und ausblick. Suchttherapie 2016; 17: 71-76 DOI: 10.1055/s-0042-100702.
• 50 Szejko N, Becher E, Heimann F. et al. Medicinal use of different cannabis strains: Results from a large prospective survey in Germany. Pharmacopsychiatry (in revision).
• 51 Strohbeck-Kühner P, Skopp G, Mattern R. Fitness to drive in spite (because) of THC. Arch Kriminol 2007; 220: 11-19
• 52 Mansell H, Quinn D, Kelly LE. et al. Cannabis for the treatment of attention deficit hyperactivity disorder: A report of 3 cases. Med Cannabis Cannabinoids 2022; 5: 1-6 DOI: 10.1159/000521370.
• 53 Milz E, Grotenhermen F. Successful therapy of treatment resistant adult ADHD with cannabis: Experience from a medical practice with 30 patients. In: Poster. Sestri Levante, Italy: 2015
• 54 Cooper RE, Williams E, Seegobin S. et al. Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. Eur Neuropsychopharmacol 2017; 27: 795-808 DOI: 10.1016/j.euroneuro.2017.05.005.
• 55 Centonze D, Bari M, Di Michele B. et al. Altered anandamide degradation in attention-deficit/hyperactivity disorder. Neurology 2009; 72: 1526-1527 DOI: 10.1212/WNL.0b013e3181a2e8f6.
• 56 Ahmadalipour A, Mehdizadeh Fanid L, Zeinalzadeh N. et al. The first evidence of an association between a polymorphism in the endocannabinoid-degrading enzyme FAAH (FAAH rs2295633) with attention deficit hyperactivity disorder. Genomics 2020; 112: 1330-1334 DOI: 10.1016/j.ygeno.2019.07.024.
• 57 Bilge S, Ekici B. CBD-enriched cannabis for autism spectrum disorder: An experience of a single center in Turkey and reviews of the literature. J Cannabis Res 2021; 3: 53 DOI: 10.1186/s42238-021-00108-7.
• 58 Bertolino B, Crupi R, Impellizzeri D. et al. Beneficial effects of co-ultramicronized palmitoylethanolamide/luteolin in a mouse model of autism and in a case report of autism. CNS Neurosci Ther 2017; 23: 87-98 DOI: 10.1111/cns.12648.
• 59 Aran A, Cassuto H, Lubotzky A. et al. Brief report: Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems-A retrospective feasibility study. J Autism Dev Disord 2019; 49: 1284-1288 DOI: 10.1007/s10803-018-3808-2.
• 60 Barchel D, Stolar O, De-Haan T. et al. Oral cannabidiol use in children with autism spectrum disorder to treat related symptoms and co-morbidities. Front Pharmacol 2018; 9: 1521 DOI: 10.3389/fphar.2018.01521.
• 61 Hacohen M, Stolar OE, Berkovitch M. et al. Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: An open label study. Transl Psychiatry 2022; 12: 375 DOI: 10.1038/s41398-022-02104-8.
• 62 Aran A, Harel M, Cassuto H. et al. Cannabinoid treatment for autism: A proof-of-concept randomized trial. Mol Autism 2021; 12: 6 DOI: 10.1186/s13229-021-00420-2.
• 63 da Silva EA, Medeiros WMB, Santos JPMD. et al. Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: Randomized, double-blind and controlled placebo clinical trial. Trends Psychiatry Psychother 2022; 26: 44 DOI: 10.47626/2237-6089-2021-0396.
• 64 Levin FR, Mariani JJ, Brooks DJ. et al. Dronabinol for the treatment of cannabis dependence: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend 2011; 116: 142-150 DOI: 10.1016/j.drugalcdep.2010.12.010.
• 65 Allsop DJ, Copeland J, Lintzeris N. et al. Nabiximols as an agonist replacement therapy during cannabis withdrawal: A randomized clinical trial. JAMA Psychiatry 2014; 71: 281-291 DOI: 10.1001/jamapsychiatry.2013.3947.
• 66 Trigo JM, Soliman A, Quilty LC. et al. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial. PLoS One 2018; 13: e0190768 DOI: 10.1371/journal.pone.0190768.
• 67 Lintzeris N, Bhardwaj A, Mills L. et al. Nabiximols for the treatment of cannabis dependence: A randomized clinical trial. JAMA Intern Med 2019; 179: 1242-1253 DOI: 10.1001/jamainternmed.2019.1993.
• 68 Freeman TP, Hindocha C, Baio G. et al. Cannabidiol for the treatment of cannabis use disorder: A phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Lancet Psychiatry 2020; 7: 865-874 DOI: 10.1016/S2215-0366(20)30290-X.
• 69 D’Souza DC, Cortes-Briones J, Creatura G. et al. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: A double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry 2019; 6: 35-45 DOI: 10.1016/S2215-0366(18)30427-9.
• 70 Lofwall MR, Babalonis S, Nuzzo PA. et al. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans. Drug Alcohol Depend 2016; 164: 143-150 DOI: 10.1016/j.drugalcdep.2016.05.002.
• 71 Bisaga A, Sullivan MA, Glass A. et al. The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone. Drug Alcohol Depend 2015; 154: 38-45 DOI: 10.1016/j.drugalcdep.2015.05.013.
• 72 Hurd YL, Spriggs S, Alishayev J. et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial. Am J Psychiatry 2019; 176: 911-922 DOI: 10.1176/appi.ajp.2019.18101191.
• 73 Kvamme SL, Pedersen MM, Rømer Thomsen K. et al. Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample. Harm Reduct J 2021; 18: 72 DOI: 10.1186/s12954-021-00520-5.
• 74 Mongeau-Pérusse V, Brissette S, Bruneau J. et al. Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: A randomized placebo-controlled trial. Addiction 2021; 116: 2431-2442 DOI: 10.1111/add.15417.
• 75 Morissette F, Mongeau-Pérusse V, Rizkallah E. et al. Exploring cannabidiol effects on inflammatory markers in individuals with cocaine use disorder: A randomized controlled trial. Neuropsychopharmacology 2021; 46: 2101-2111 DOI: 10.1038/s41386-021-01098-z.
• 76 Fernandes JAB, Filev R, Fidalgo TM. Cannabinoids for substance use disorder treatment: What does the current evidence say?. Cannabis Cannabinoid Res 2023; 8: 703-715 DOI: 10.1089/can.2023.0065.
• 77 Cannabinoid Conference 2022. Med Cannabis Cannabinoids. 2022; 5: 159-198 DOI: 10.1159/000527113.
• 78 Botsford SL, Yang S, George TP. Cannabis and cannabinoids in mood and anxiety disorders: Impact on illness onset and course, and assessment of therapeutic potential. Am J Addict 2020; 29: 9-26 DOI: 10.1111/ajad.12963.
• 79 Sexton M, Cuttler C, Finnell JS. et al. A cross-sectional survey of medical cannabis users: Patterns of use and perceived efficacy. Cannabis Cannabinoid Res 2016; 1: 131-138 DOI: 10.1089/can.2016.0007.
• 80 Li X, Diviant JP, Stith SS. et al. The effectiveness of cannabis flower for immediate relief from symptoms of depression. Yale J Biol Med 2020; 93: 251-264
• 81 Ware MA, Wang T, Shapiro S. et al. Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. CMAJ 2010; 182: E694-E701 DOI: 10.1503/cmaj.091414.
• 82 Emons B, Arning L, Makulla V-E. et al. Endocannabinergic modulation of central serotonergic activity in healthy human volunteers. Ann Gen Psychiatry 2023; 22: 11 DOI: 10.1186/s12991-023-00437-2.
• 83 Szejko N, Fremer C, Müller-Vahl KR. Cannabis improves obsessive-compulsive disorder-case report and review of the literature. Front Psychiatry 2020; 11: 681 DOI: 10.3389/fpsyt.2020.00681.
• 84 Kayser RR, Senter MS, Tobet R. et al. Patterns of cannabis use among individuals with obsessive-compulsive disorder: Results from an internet survey. J Obsessive Compuls Relat Disord 2021; 30: 100664 DOI: 10.1016/j.jocrd.2021.100664.
• 85 Schindler F, Anghelescu I, Regen F. et al. Improvement in refractory obsessive compulsive disorder with dronabinol. Am J Psychiatry 2008; 165: 536-537 DOI: 10.1176/appi.ajp.2007.07061016.
• 86 Cooper JJ, Grant J. Refractory OCD due to thalamic infarct with response to dronabinol. J Neuropsychiatry Clin Neurosci 2017; 29: 77-78 DOI: 10.1176/appi.neuropsych.16030053.
• 87 Kayser RR, Haney M, Raskin M. et al. Acute effects of cannabinoids on symptoms of obsessive-compulsive disorder: A human laboratory study. Depress Anxiety 2020; 37: 801-811 DOI: 10.1002/da.23032.
• 88 Grant JE, Odlaug BL, Chamberlain SR. et al. Dronabinol, a cannabinoid agonist, reduces hair pulling in trichotillomania: A pilot study. Psychopharmacology (Berl) 2011; 218: 493-502 DOI: 10.1007/s00213-011-2347-8.
• 89 Grant JE, Valle S, Chesivoir E. et al. Tetrahydrocannabinol fails to reduce hair pulling or skin picking: Results of a double-blind, placebo-controlled study of dronabinol. Int Clin Psychopharmacol 2022; 37: 14-20 DOI: 10.1097/YIC.0000000000000382.
• 90 Abizaid A, Merali Z, Anisman H. Cannabis: A potential efficacious intervention for PTSD or simply snake oil?. J Psychiatry Neurosci 2019; 44: 75-78 DOI: 10.1503/jpn.190021.
• 91 Wilkinson ST, Stefanovics E, Rosenheck RA. Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with posttraumatic stress disorder. J Clin Psychiatry 2015; 76: 1174-1180 DOI: 10.4088/JCP.14m09475.
• 92 Metrik J, Stevens AK, Gunn RL. et al. Cannabis use and posttraumatic stress disorder: Prospective evidence from a longitudinal study of veterans. Psychol Med 2022; 52: 446-456 DOI: 10.1017/S003329172000197X.
• 93 Allan NP, Ashrafioun L, Kolnogorova K. et al. Interactive effects of PTSD and substance use on suicidal ideation and behavior in military personnel: Increased risk from marijuana use. Depress Anxiety 2019; 36: 1072-1079 DOI: 10.1002/da.22954.
• 94 LaFrance EM, Glodosky NC, Bonn-Miller M. et al. Short and long-term effects of cannabis on symptoms of post-traumatic stress disorder. J Affect Disord 2020; 274: 298-304 DOI: 10.1016/j.jad.2020.05.132.
• 95 Lake S, Kerr T, Buxton J. et al. Does cannabis use modify the effect of post-traumatic stress disorder on severe depression and suicidal ideation? Evidence from a population-based cross-sectional study of Canadians. J Psychopharmacol 2020; 34: 181-188 DOI: 10.1177/0269881119882806.
• 96 Passie T, Emrich HM, Karst M. et al. Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Test Anal 2012; 4: 649-659 DOI: 10.1002/dta.1377.
• 97 Greer GR, Grob CS, Halberstadt AL. PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program. J Psychoactive Drugs 2014; 46: 73-77 DOI: 10.1080/02791072.2013.873843.
• 98 Nacasch N, Avni C, Toren P. Medical cannabis for treatment-resistant combat PTSD. Front Psychiatry 2022; 13: 1014630 DOI: 10.3389/fpsyt.2022.1014630.
• 99 Cameron C, Watson D, Robinson J. Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: A retrospective evaluation. J Clin Psychopharmacol 2014; 34: 559-564 DOI: 10.1097/JCP.0000000000000180.
• 100 Fraser GA. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci Ther 2009; 15: 84-88 DOI: 10.1111/j.1755-5949.2008.00071.x.
• 101 Roitman P, Mechoulam R, Cooper-Kazaz R. et al. Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin Drug Investig 2014; 34: 587-591 DOI: 10.1007/s40261-014-0212-3.
• 102 Shannon S, Opila-Lehman J. Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: A case report. Perm J 2016; 20: 16-005 DOI: 10.7812/TPP/16-005.
• 103 Elms L, Shannon S, Hughes S. et al. Cannabidiol in the treatment of post-traumatic stress disorder: A case series. J Altern Complement Med 2019; 25: 392-397 DOI: 10.1089/acm.2018.0437.
• 104 Jetly R, Heber A, Fraser G. et al. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology 2015; 51: 585-588 DOI: 10.1016/j.psyneuen.2014.11.002.
• 105 Bolsoni LM, Crippa JAS, Hallak JEC. et al. The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event. Braz J Psychiatry 44: 298-307 DOI: 10.1590/1516-4446-2021-2317.
• 106 Bolsoni LM, Crippa JAS, Hallak JEC. et al. Effects of cannabidiol on symptoms induced by the recall of traumatic events in patients with posttraumatic stress disorder. Psychopharmacology 2022; 239: 1499-1507 DOI: 10.1007/s00213-021-06043-y.
• 107 Bonn-Miller MO, Sisley S, Riggs P. et al. The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial. PLoS One 2021; 16: e0246990 DOI: 10.1371/journal.pone.0246990.
• 108 Neumeister A, Normandin MD, Pietrzak RH. et al. Elevated brain cannabinoid CB1 receptor availability in posttraumatic stress disorder: A positron emission tomography study. Mol Psychiatry 2013; 18: 1034-1040 DOI: 10.1038/mp.2013.61.
• 109 Piper BJ. Mother of cerries, ACDC, or chocolope: Examination of the strains used by medical cannabis patients in New England. J Psychoactive Drugs 2018; 50: 95-104 DOI: 10.1080/02791072.2017.1390179.
• 110 Kuhathasan N, Dufort A, MacKillop J. et al. The use of cannabinoids for sleep: A critical review on clinical trials. Exp Clin Psychopharmacol 2019; 27: 383-401 DOI: 10.1037/pha0000285.
• 111 Peball M, Seppi K, Krismer F. et al. Effects of nabilone on sleep outcomes in patients with Parkinson’s disease: A post-hoc analysis of NMS-Nab study. Mov Disord Clin Pract 2022; 9: 751-758 DOI: 10.1002/mdc3.13471.
• 112 Maddison KJ, Kosky C, Walsh JH. Is there a place for medicinal cannabis in treating patients with sleep disorders?. What we know so far. Nat Sci Sleep 2022; 14: 957-968 DOI: 10.2147/NSS.S340949.
• 113 Walsh JH, Maddison KJ, Rankin T. et al. Treating insomnia symptoms with medicinal cannabis: A randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo. Sleep 2021; 44: zsab149 DOI: 10.1093/sleep/zsab149.
• 114 Ried K, Tamanna T, Matthews S. et al. Medicinal cannabis improves sleep in adults with insomnia: A randomised double-blind placebo-controlled crossover study. J Sleep Res 2023; 32: e13793 DOI: 10.1111/jsr.13793.
• 115 Sandyk R, Awerbuch G. Marijuana and Tourette’s syndrome. J Clin Psychopharmacol 1988; 8: 444-445
• 116 Hemming M, Yellowlees PM. Effective treatment of Tourette’s syndrome with marijuana. J Psychopharmacol (Oxford) 1993; 7: 389-391 DOI: 10.1177/026988119300700411.
• 117 Müller-Vahl KR, Kolbe H, Schneider U. et al. Cannabinoids: Possible role in patho-physiology and therapy of Gilles de la Tourette syndrome. Acta Psychiatr Scand 1998; 98: 502-506
• 118 Abi-Jaoude E, Chen L, Cheung P. et al. Preliminary evidence on cannabis effectiveness and tolerability for adults with Tourette syndrome. J Neuropsychiatry Clin Neurosci 2017; 29: 391-400 DOI: 10.1176/appi.neuropsych.16110310.
• 119 Thaler A, Arad S, Schleider LB-L. et al. Single center experience with medical cannabis in Gilles de la Tourette syndrome. Parkinsonism & Related Disorders 2019; 61: 211-213 DOI: 10.1016/j.parkreldis.2018.10.004.
• 120 Jakubovski E, Müller-Vahl K. Speechlessness in Gilles de la Tourette syndrome: Cannabis-based medicines improve severe vocal blocking tics in two patients. Int J Mol Sci 2017; 18: 1739 DOI: 10.3390/ijms18081739.
• 121 Müller-Vahl KR, Schneider U, Kolbe H. et al. Treatment of Tourette’s syndrome with delta-9-tetrahydrocannabinol. Am J Psychiatry 1999; 156: 495
• 122 Müller-Vahl K, Schneider U, Emrich H. Combined treatment of Tourette-syndrome with delts-9-THC and dopamine receptor antagonists. J Cannabis Therap 2002; 2: 145-154
• 123 Brunnauer A, Segmiller FM, Volkamer T. et al. Cannabinoids improve driving ability in a Tourette’s patient. Psychiatry Res 2011; 190: 382 DOI: 10.1016/j.psychres.2011.05.033.
• 124 Pichler E-M, Kawohl W, Seifritz E. et al. Pure delta-9-tetrahydrocannabinol and its combination with cannabidiol in treatment-resistant Tourette syndrome: A case report. Int J Psychiatry Med 2019; 54: 150-156 DOI: 10.1177/0091217418791455.
• 125 Trainor D, Evans L, Bird R. Severe motor and vocal tics controlled with Sativex®. Australas Psychiatry 2016; 24: 541-544 DOI: 10.1177/1039856216663737.
• 126 Kanaan AS, Jakubovski E, Müller-Vahl K. Significant tic reduction in an otherwise treatment-resistant patient with Gilles de la Tourette syndrome following treatment with nabiximols. Brain Sci 2017; 7: 47 DOI: 10.3390/brainsci7050047.
• 127 Bloch MH, Landeros-Weisenberger A, Johnson JA. et al. A phase-2 pilot study of a therapeutic combination of Δ9-tetrahydracannabinol and palmitoylethanolamide for adults with Tourette’s syndrome. J Neuropsychiatry Clin Neurosci 2021; 33: 328-336 DOI: 10.1176/appi.neuropsych.19080178.
• 128 Milosev LM, Psathakis N, Szejko N. et al. Treatment of Gilles de la Tourette syndrome with cannabis-based medicine: Results from a retrospective analysis and online survey. Cannabis Cannabinoid Res 2019; 4: 265-274 DOI: 10.1089/can.2018.0050.
• 129 Szejko N, Jakubovski E, Fremer C. et al. Delta-9-tetrahydrocannabinol for the treatment of a child with Tourette syndrome—case report. EJMCR 2018; 2: 43-46
• 130 Szejko N, Jakubovski E, Fremer C. et al. Vaporized cannabis is effective and well-tolerated in an adolescent with Tourette syndrome. MCA 2019; 2: 60-64 DOI: 10.1159/000496355.
• 131 Hasan A, Rothenberger A, Münchau A. et al. Oral delta 9-tetrahydrocannabinol improved refractory Gilles de la Tourette syndrome in an adolescent by increasing intracortical inhibition: A case report. J Clin Psychopharmacol 2010; 30: 190-192 DOI: 10.1097/JCP.0b013e3181d236ec.
• 132 Müller-Vahl KR, Schneider U, Koblenz A. et al. Treatment of Tourette’s syndrome with delta 9-tetrahydrocannabinol (THC): A randomized crossover trial. Pharmacopsychiatry 2002; 35: 57-61 DOI: 10.1055/s-2002-25028.
• 133 Müller-Vahl KR, Schneider U, Prevedel H. et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: A 6-week randomized trial. J Clin Psychiatry 2003; 64: 459-465
• 134 Müller-Vahl KR, Koblenz A, Jöbges M. et al. Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Pharmacopsychiatry 2001; 34: 19-24 DOI: 10.1055/s-2001-15191.
• 135 Müller-Vahl KR, Prevedel H, Theloe K. et al. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): No influence on neuropsychological performance. Neuropsychopharmacology 2003; 28: 384-388 DOI: 10.1038/sj.npp.1300047.
• 136 Abi-Jaoude E, Bhikram T, Parveen F. et al. A double-blind, randomized, controlled crossover trial of cannabis in adults with Tourette syndrome. Cannabis Cannabinoid Res 2023; 8: 835-845 DOI: 10.1089/can.2022.0091.
• 137 Jakubovski E, Pisarenko A, Fremer C. et al. The CANNA-TICS Study Protocol: A randomized multi-center double-blind placebo controlled trial to demonstrate the efficacy and safety of nabiximols in the treatment of adults with chronic tic disorders. Front Psychiatry 2020; 11: 575826 DOI: 10.3389/fpsyt.2020.575826.
• 138 Müller-Vahl KR, Pisarenko A, Szejko N. et al. CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders – Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study. Psychiatry Res 2023; 323: 115135 DOI: 10.1016/j.psychres.2023.115135.
• 139 Müller-Vahl KR, Fremer C, Beals C. et al. Endocannabinoid modulation using monoacylglycerol lipase inhibition in Tourette syndrome: A phase 1 randomized, placebo-controlled study. Pharmacopsychiatry 2022; 55: 148-156 DOI: 10.1055/a-1675-3494.
• 140 Müller-Vahl KR, Fremer C, Beals C. et al. Monoacylglycerol Lipase Inhibition in Tourette syndrome: A 12-week, randomized, controlled study. Mov Disord 2021; 36: 2413-2418 DOI: 10.1002/mds.28681.
• 141 Gadzicki D, Müller-Vahl KR, Heller D. et al. Tourette syndrome is not caused by mutations in the central cannabinoid receptor (CNR1) gene. Am J Med Genet B Neuropsychiatr Genet 2004; 127B: 97-103 DOI: 10.1002/ajmg.b.20159.
• 142 Szejko N, Fichna JP, Safranow K. et al. Association of a variant of CNR1 gene encoding cannabinoid receptor 1 with Gilles de la Tourette syndrome. Front Genet 2020; 11: 125 DOI: 10.3389/fgene.2020.00125.