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Brain Sciences
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Cannabis and the Brain: Novel Perspectives and Understandings
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Cannabis and the Brain: Novel Perspectives and Understandings

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropsychiatry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 45493

Special Issue Editors

Dr. Justin Matheson

E-Mail Website
Guest Editor
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
Interests: Cannabis; substance use disorders; clinical trials; human behavioral pharmacology; sex/gender differences
Dr. Catharine Mielnik

E-Mail Website
Co-Guest Editor
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
Interests: cannabinoids; small molecule pre-clinical validation; murine models of psychiatric disor-ders; psychosis; schizophrenia; autism

Special Issue Information

Dear Colleagues,

Global changes in the legal status of cannabis have led to shifts in the prevalence of cannabis use and attitudes towards cannabis, as well as increased interest in cannabinoids as potential therapeutics. Cannabis use is associated with acute and long-term harm, including adverse cognitive effects, cannabis use disorder, and an increased risk of mood, anxiety, and psychotic disorders. At the same time, cannabis and related cannabinoid compounds have shown some promise in potentially treating symptoms of numerous brain disorders, including neurological disorders such as Parkinson’s disease and psychiatric disorders such as post-traumatic stress disorder.

This Special Issue will present novel perspectives on relationships between cannabis and the brain, both in the context of non-medical (recreational) use and potential therapeutic applications of cannabinoids. We are seeking both original research papers and review articles that further our understanding of cannabis–brain relationships, with a focus on (1) adverse effects of cannabis on brain structure and/or function, including discussion of relevant risk or protective factors; or (2) evidence of amelioration of brain structure and/or function in pathological states that supports the therapeutic use of cannabinoids to treat brain disorders.

Dr. Justin Matheson
Dr. Catharine Mielnik
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cannabis
  • Cannabinoid
  • brain
  • psychiatric disorders
  • substance use disorders
  • neurological disorders
  • cognition

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Published Papers (8 papers)

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Research

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14 pages, 680 KiB  
Article
Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder—Preliminary Findings
by Nadia Boachie, Erin Gaudette, Richard P. Bazinet, Lin Lin, Rachel F. Tyndale, Esmaeil Mansouri, Marilyn A. Huestis, Junchao Tong, Bernard Le Foll, Stephen J. Kish, Tony P. George and Isabelle Boileau
Brain Sci. 2023, 13(10), 1375; https://doi.org/10.3390/brainsci13101375 - 27 Sep 2023
Cited by 7 | Viewed by 2446
Abstract
Background: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis [...] Read more.
Background: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. Methods: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography–mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). Results: In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31–40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = −0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. Conclusions: Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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22 pages, 5988 KiB  
Article
Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress
by Hye Ji J. Kim, Ayat Zagzoog, Costanza Ceni, Rebecca Ferrisi, Nicola Janz and Robert B. Laprairie
Brain Sci. 2023, 13(2), 314; https://doi.org/10.3390/brainsci13020314 - 13 Feb 2023
Cited by 3 | Viewed by 2737
Abstract
The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience [...] Read more.
The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience pleasure from natural rewards. In the current study, a 24 h restraint stress test (24 h RST) reduced sucrose preference in adult male and female C57BL/6 mice. Prior to the stressor, subsets of mice were intraperitoneally administered cannabinoid and orexin receptor agonists, antagonists, and combinations of these drugs. Restraint mice that received the cannabinoid receptor type 1 (CB1R) antagonist SR141716A, orexin receptor type 2 (OX2R) agonist YNT-185, and the combination of SR141716A and YNT-185, exhibited less anhedonia compared to vehicle/control mice. Thus, the 24 h RST likely decreased orexin signaling, which was then restored by YNT-185. Receptor colocalization analysis throughout mesocorticolimbic brain regions revealed increased CB1R-OX1R colocalization from SR141716A and YNT-185 treatments. Although a previous study from our group showed additive cataleptic effects between CP55,940 and the dual orexin receptor antagonist (TCS-1102), the opposite combination of pharmacological agents proved additive for sucrose preference. Taken together, these results reveal more of the complex interactions between the endocannabinoid and orexin systems. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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11 pages, 1214 KiB  
Article
Cannabis-Based Medicinal Products in the Management of Emotionally Unstable Personality Disorder (EUPD): A Narrative Review and Case Series
by Waseem Sultan, Anup Mathew, Matthew R. D. Brown, Juan F. Gálvez-Flórez and Guillermo Moreno-Sanz
Brain Sci. 2022, 12(11), 1467; https://doi.org/10.3390/brainsci12111467 - 29 Oct 2022
Viewed by 9275
Abstract
Emotionally unstable personality disorder (EUPD) is a common mental health disorder, manifesting with a range of chronic and debilitating symptoms, including impaired social functioning, unstable mood, and risky impulsive or self-injurious behaviour. Whilst the exact aetiology has not been fully elucidated, implicated factors [...] Read more.
Emotionally unstable personality disorder (EUPD) is a common mental health disorder, manifesting with a range of chronic and debilitating symptoms, including impaired social functioning, unstable mood, and risky impulsive or self-injurious behaviour. Whilst the exact aetiology has not been fully elucidated, implicated factors seem to include genetic factors, environmental causes such as trauma, and neurotransmitter deficits. The literature suggests that impaired functioning of the endocannabinoid system in key brain regions responsible for emotional processing and stress response may underlie the manifestation of EUPD symptoms. The National Institute for Health and Care Excellence (NICE) 2009 guidelines state that “no drugs have established efficacy in treating or managing EUPD”, and yet, patients are commonly prescribed medication which includes antipsychotics, antidepressants, and mood stabilisers. Here we present a case series of seven participants diagnosed with EUPD and treated with cannabis-based medicinal products (CBMPs). Participants were given an initial assessment and followed up one month after CBMPs prescription. Improvement in symptoms was assessed by the completion of ratified rating scales by the participant and psychiatrist. Our results indicate that CBMPs were effective and well tolerated, as six participants reported a noticeable improvement in their symptoms and functioning. Although promising, further research is needed to ascertain the long-term tolerability, efficacy, and dosing strategy for CBMPs in EUPD. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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11 pages, 917 KiB  
Article
Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults
by Justin Matheson, Yollanda J. Zhang, Bruna Brands, Christine M. Wickens, Arun K. Tiwari, Clement C. Zai, James L. Kennedy and Bernard Le Foll
Brain Sci. 2022, 12(9), 1189; https://doi.org/10.3390/brainsci12091189 - 3 Sep 2022
Cited by 3 | Viewed by 2510
Abstract
Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using [...] Read more.
Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using data from 48 young adults (aged 19–25 years) reporting 1–4 days of cannabis use per week who completed a placebo-controlled human laboratory experiment, we tested the hypothesis that the rs2235048 polymorphism of ABCB1 would influence acute responses to smoked cannabis. C-allele carriers reported on average greater frequency of weekly cannabis use compared to the TT genotype carriers (TC/CC mean ± SEM = 2.74 ± 0.14, TT = 1.85 ± 0.24, p = 0.004). After smoking a single cannabis cigarette to their desired high, C-allele carriers had higher area-under-the-curve (AUC) of both THC metabolites (11-OH-THC TC/CC = 7.18 ± 9.64, TT = 3.28 ± 3.40, p = 0.05; THC-COOH TC/CC = 95.21 ± 116.12, TT = 45.92 ± 42.38, p = 0.043), and these results were impact by self-reported ethnicity. There were no significant differences in self-reported subjective drug effects except for a greater AUC of visual analogue scale rating of drug liking (TC/CC = 35,398.33 ± 37,233.72, TT = 15,895.56 ± 13,200.68, p = 0.017). Our preliminary findings suggest that further work in a larger sample should investigate whether human ABCB1 influences cannabis-related phenotypes and plays a role in the risk of developing a cannabis use disorder. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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Review

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17 pages, 989 KiB  
Review
Neuromodulation for Cannabis Use: A Scoping Review
by Anthony Ngoy, Victor M. Tang, Kebin Xiao, Daniel M. Blumberger, Tony P. George, Joshua L. Gowin, Bernard Le Foll and Matthew E. Sloan
Brain Sci. 2024, 14(4), 356; https://doi.org/10.3390/brainsci14040356 - 2 Apr 2024
Cited by 1 | Viewed by 3184
Abstract
This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. [...] Read more.
This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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24 pages, 1282 KiB  
Review
Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review
by Ahmed Hasbi, Bertha K. Madras and Susan R. George
Brain Sci. 2023, 13(2), 325; https://doi.org/10.3390/brainsci13020325 - 14 Feb 2023
Cited by 32 | Viewed by 10146
Abstract
Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to [...] Read more.
Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components—tetrahydrocannabinol (THC) and cannabidiol (CBD)—or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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Other

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18 pages, 1979 KiB  
Systematic Review
Risk of Motor Vehicle Collisions and Culpability among Older Drivers Using Cannabis: A Meta-Analysis
by Arun Chinna-Meyyappan, Hui Jue Wang, Kritleen K. Bawa, Edward Ellazar, Emilie Norris-Roozmon, Gary Naglie, Nathan Herrmann, Judith L. Charlton, Sjaan Koppel, Saulo Castel, Krista L. Lanctôt and Mark J. Rapoport
Brain Sci. 2023, 13(3), 421; https://doi.org/10.3390/brainsci13030421 - 28 Feb 2023
Viewed by 9021
Abstract
Limited studies have investigated the effects of cannabis use on driving among older adults, who represent the fastest growing segment of drivers globally. We conducted a systematic review and meta-analysis to evaluate the effects of delta-9-tetrahydrocannabinol (THC) exposure on risks of (1) motor [...] Read more.
Limited studies have investigated the effects of cannabis use on driving among older adults, who represent the fastest growing segment of drivers globally. We conducted a systematic review and meta-analysis to evaluate the effects of delta-9-tetrahydrocannabinol (THC) exposure on risks of (1) motor vehicle collisions (MVC) and (2) culpability for MVCs among adults 50 years and older. Three reviewers screened 7022 studies identified through MEDLINE, EMBASE, CENTRAL, and PsycINFO. Odds Ratios (OR) were calculated using the Mantel-Haenszel method in Review Manager 5.4.1. Heterogeneity was assessed using I2. The National Heart, Lung, and Blood Institute tool was used to assess the quality of each study. Seven cross-sectional studies were included. Three studies evaluated culpability while four evaluated MVC. The pooled risk of MVC was not significantly different between THC-positive and THC-negative older drivers (OR, 95% CI 1.15 [0.40, 3.31]; I2 = 72%). In culpability studies, THC exposure was not significantly associated with an increased risk of being culpable for MVC among adults over the age of 50 (OR, 95% CI 1.24 [0.95, 1.61]; I2 = 0%). Inspection of funnel plots did not indicate publication bias. Our review found that THC exposure was not associated with MVC involvement nor with culpability for MVCs. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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12 pages, 692 KiB  
Systematic Review
Contingency Management for Treatment of Cannabis Use Disorder in Co-Occurring Mental Health Disorders: A Systematic Review
by Justyne D. Rodas, Maryam Sorkhou and Tony P. George
Brain Sci. 2023, 13(1), 36; https://doi.org/10.3390/brainsci13010036 - 23 Dec 2022
Cited by 9 | Viewed by 4056
Abstract
Amongst individuals with a mental health disorder, a comorbid diagnosis of cannabis use disorder (CUD) is associated with numerous adverse consequences, including more severe symptom profiles, poorer treatment response, and reduced psychosocial functioning. Contingency management (CM), a method to specifically reinforce target behavior [...] Read more.
Amongst individuals with a mental health disorder, a comorbid diagnosis of cannabis use disorder (CUD) is associated with numerous adverse consequences, including more severe symptom profiles, poorer treatment response, and reduced psychosocial functioning. Contingency management (CM), a method to specifically reinforce target behavior attainment (e.g., substance use abstinence), may provide an effective intervention in treating cannabis use in patients with a dual diagnosis of CUD and a mental health disorder. A systematic search examining the effects of CM on cannabis use, clinical, cognitive, and psychosocial outcomes in patients with a mental health disorder on PubMed, PsycINFO, and EMBASE databases up to November 2022 was performed. Six studies met inclusion criteria for our review. We found CM to be efficacious in producing cannabis use reductions and abstinence amongst individuals with a psychotic-spectrum or major depressive disorder. Additional longitudinal studies with larger sample sizes, other psychiatric populations, and longer follow-up periods are needed to evaluate the sustained effects of CM. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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