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Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior

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

Deadline for manuscript submissions: closed (15 May 2020) | Viewed by 71139

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Dr. Marco Colizzi

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Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Interests: psychosis; neuropsychopharmacology; brain imaging; cannabinoids; cognitive neuroscience
Special Issues, Collections and Topics in MDPI journals

Dr. Sagnik Bhattacharyya

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Dear Colleagues,

Over the years, there has been increasing interest into the public health impact of cannabis use, especially by young adults. This follows the evidence of a growing prevalence of regular cannabis use worldwide, with approximately 200 million users. Recreational cannabis use, especially a frequent use of products with high levels of its main psychoactive ingredient delta-9-tetrahydrocannabinol (Δ 9-THC), can cause dependence and have transient and long-lasting detrimental mental health effects, also negatively impacting cognitive processing and brain function and metabolism. In regular users, the development of tolerance to some of the effects of cannabis, especially the pleasurable ones, may lead to progressively heavier use in order to obtain the same effects in terms of their intensity, with higher health risks. However, the Cannabis Sativa plant contains different chemicals with different potential effects. In this regard, cannabidiol has gained interest because of its potential therapeutic properties, in line with evidence that CBD and Δ9-THC may exhibit opposite effects at the cannabinoid receptor type 1 (CB1), Δ9-THC being a partial agonist and CBD an antagonist/inverse agonist.

Different cannabinoids may modulate human brain function and behavior in different ways, with different risk–benefit profiles. Original research articles advancing our understanding of the “Neuropsychiatry and Brain effects of Cannabis” are solicited for this Special Issue. Reviews providing an analytical perspective on the existing literature are also welcome.

Dr. Marco Colizzi
Dr. Sagnik Bhattacharyya
Guest Editors

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Keywords

Cannabinoids
Delta-9-tetrahydrocannabinol
Cannabidiol
Cannabis use disorders
Dependence
Tolerance
Neuropsychiatric disorders
Cognition
Neurophysiology
Neurochemistry

Published Papers (13 papers)

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Editorial

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5 pages, 203 KiB

Open AccessEditorial

Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior

by Marco Colizzi and Sagnik Bhattacharyya

Brain Sci. 2020, 10(11), 834; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10110834 - 10 Nov 2020

Cited by 5 | Viewed by 2777

Abstract

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(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

4 pages, 194 KiB

Open AccessEditorial

Cannabis and Cognition: Connecting the Dots towards the Understanding of the Relationship

by Marco Colizzi, Sarah Tosato and Mirella Ruggeri

Brain Sci. 2020, 10(3), 133; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030133 - 27 Feb 2020

Cited by 4 | Viewed by 3752

Abstract

Several studies have advanced the understanding of the effects of cannabis on cognitive function. A comprehensive reappraisal of such literature may help in drawing conclusions about the potential risks associated with cannabis use. In summary, the evidence suggests that earlier age of use, high-frequency and high-potency cannabis use, as well as sustained use over time and use of synthetic cannabinoids, are all correlated with a higher likelihood of developing potentially severe and persistent executive function impairments. While the exact mechanisms underlying the adverse effects of cannabis on cognition are not completely clear, Magnetic Resonance Imaging (MRI) studies support the presence of both structural and functional alterations associated with cannabis use. Cognitive dysfunction is also a core feature of many neuropsychiatric disorders and care must be taken regarding the effects of cannabis use in these patient populations. Cognitive impairments affect patients’ daily functions, sociability, and long-term outcome, posing elevated economic, social, and clinical burdens. There is, thus, a compelling case for implementing behavioral and cognitive rehabilitation therapies for these patients, as well as investigating the endocannabinoid system in the development of new psychopharmacological treatments. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

Research

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15 pages, 2160 KiB

Open AccessArticle

Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

by Joshua Aviram, Yelena Vysotski, Paula Berman, Gil M. Lewitus, Elon Eisenberg and David Meiri

Brain Sci. 2020, 10(6), 360; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10060360 - 09 Jun 2020

Cited by 17 | Viewed by 15640

Abstract

Background: Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency. Methods: Participants were migraine patients licensed for MC treatment. Data included self-reported questionnaires and MC treatment features. Patients were retrospectively classified as responders vs. non-responders (≥50% vs. <50% decrease in monthly migraine attacks frequency following MC treatment initiation, respectively). Comparative statistics evaluated differences between these two subgroups. Results: A total of 145 patients (97 females, 67%) with a median MC treatment duration of three years were analyzed. Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05–0.72); p < 0.05, respectively). Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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17 pages, 1502 KiB

Open AccessArticle

Do Adolescents Use Substances to Relieve Uncomfortable Sensations? A Preliminary Examination of Negative Reinforcement among Adolescent Cannabis and Alcohol Users

by April C. May, Joanna Jacobus, Jennifer L. Stewart, Alan N. Simmons, Martin P. Paulus and Susan F. Tapert

Brain Sci. 2020, 10(4), 214; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10040214 - 05 Apr 2020

Cited by 6 | Viewed by 3546

Abstract

Alcohol and cannabis use are highly prevalent among adolescents and associated with negative consequences. Understanding motivations behind substance use in youth is important for informing prevention and intervention efforts. The present study aims to examine negative reinforcement principles of substance use among adolescent cannabis and alcohol users by pairing a cue reactivity paradigm with an aversive interoceptive stimulus. Adolescents (ages 15–17), classified as controls (CTL; n = 18), cannabis and/or alcohol experimenters (CAN+ALC-EXP; n = 16), or individuals meeting clinical criteria for cannabis and/or alcohol use disorder (CAN+ALC-SUD; n = 13) underwent functional magnetic resonance imaging during which they experienced an aversive interoceptive probe delivered via breathing load while simultaneously performing a cue reactivity paradigm. Participants also provided self-report ratings of how their substance use is positively or negatively reinforced. While experiencing the breathing load, CAN+ALC-SUD exhibited greater (p < 0.05) deactivation in the right amygdala, the left inferior frontal gyrus, and the left parahippocampal gyrus than CAN+ALC-EXP and CTL, who did not differ. Across all substance users, activation during the breathing load within the left parahippocampal gyrus negatively correlated with cannabis and alcohol lifetime use episodes and the left inferior frontal gyrus activity negatively correlated with lifetime alcohol use episodes. CAN+ALC-SUD reported experiencing more positive and negative reinforcement of using their substance of choice than CAN+ALC-EXP; both user groups reported higher levels of positive than negative reinforcement. Adolescents with a cannabis/alcohol use disorder demonstrate an altered response to interoceptive perturbations. However, adolescent cannabis/alcohol use does not appear to be driven by negative reinforcement, as viewing substance images did not dampen this response. Based on self-report data, the experience of positive reinforcement may be stronger for adolescents. Future studies should examine whether positive reinforcement contributes to adolescent substance use. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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9 pages, 430 KiB

Open AccessArticle

Efficacy of Dronabinol for Acute Pain Management in Adults with Traumatic Injury: Study Protocol of A Randomized Controlled Trial

by Claire Swartwood, Kristin Salottolo, Robert Madayag and David Bar-Or

Brain Sci. 2020, 10(3), 161; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030161 - 12 Mar 2020

Cited by 5 | Viewed by 3508

Abstract

Delta-9-tetrahydrocannabinol (Δ⁹-THC) and other cannabinoids present in cannabis (marijuana) have been shown to affect the normal inhibitory pathways that influence nociception in humans. The potential benefits of cannabinoids as an analgesic are likely greatest in hyperalgesic and inflammatory states, suggesting a role as a therapeutic agent for treating acute pain following injury. Dronabinol is a licensed form of Δ⁹-THC. The primary objective of this single center randomized controlled trial is to evaluate the efficacy of adjunctive dronabinol versus control (systemic analgesics only, no dronabinol) for reducing opioid consumption in adults with traumatic injury. Study inclusion is based on high baseline utilization of opioids ≥50 morphine equivalents (mg) within 24 h of admission for adults aged 18–65 years with traumatic injury. There is a 48-hour screening period followed by a 48-hour treatment period after randomization. A total of 122 patients will be randomized 1:1 across 2 study arms: adjunctive dronabinol versus control (standard of care using systemic analgesics, no adjunctive dronabinol). Patients randomized to the dronabinol arm should receive their first dose within 12 h of randomization, with a dose range of 5 mg up to 30 mg daily in divided doses, in addition to systemic analgesics as needed for pain. The primary efficacy endpoint is a change in opioid consumption (morphine equivalents), assessed post-randomization (48 h after randomization) minus pre-randomization (24 h prior to randomization). This is the first randomized trial to investigate whether adjunctive dronabinol is effective in reducing opioid consumption in acute pain management of traumatic injury. Trial Registration: ClinicalTrials.gov Identifier: NCT03928015. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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17 pages, 1617 KiB

Open AccessArticle

Increased Resting State Triple Network Functional Connectivity in Undergraduate Problematic Cannabis Users: A Preliminary EEG Coherence Study

by Claudio Imperatori, Chiara Massullo, Giuseppe Alessio Carbone, Angelo Panno, Marta Giacchini, Cristina Capriotti, Elisa Lucarini, Benedetta Ramella Zampa, Eric Murillo-Rodríguez, Sérgio Machado and Benedetto Farina

Brain Sci. 2020, 10(3), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030136 - 28 Feb 2020

Cited by 19 | Viewed by 4346

Abstract

An increasing body of experimental data have suggested that aberrant functional interactions between large-scale networks may be the most plausible explanation of psychopathology across multiple mental disorders, including substance-related and addictive disorders. In the current research, we have investigated the association between problematic cannabis use (PCU) and triple-network electroencephalographic (EEG) functional connectivity. Twelve participants with PCU and 24 non-PCU participants were included in the study. EEG recordings were performed during resting state (RS). The exact Low-Resolution Electromagnetic Tomography software (eLORETA) was used for all EEG analyses. Compared to non-PCU, PCU participants showed an increased delta connectivity between the salience network (SN) and central executive network (CEN), specifically, between the dorsal anterior cingulate cortex and right posterior parietal cortex. The strength of delta connectivity between the SN and CEN was positively and significantly correlated with higher problematic patterns of cannabis use after controlling for age, sex, educational level, tobacco use, problematic alcohol use, and general psychopathology (r_p = 0.40, p = 0.030). Taken together, our results show that individuals with PCU could be characterized by a specific dysfunctional interaction between the SN and CEN during RS, which might reflect the neurophysiological underpinnings of attentional and emotional processes of cannabis-related thoughts, memories, and craving. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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21 pages, 5529 KiB

Open AccessArticle

Assessing the Role of Cannabis Use on Cortical Surface Structure in Adolescents and Young Adults: Exploring Gender and Aerobic Fitness as Potential Moderators

by Ryan M. Sullivan, Alexander L. Wallace, Natasha E. Wade, Ann M. Swartz and Krista M. Lisdahl

Brain Sci. 2020, 10(2), 117; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020117 - 22 Feb 2020

Cited by 9 | Viewed by 4234

Abstract

Cannabis use in adolescents and young adults is linked with aberrant brain structure, although findings to date are inconsistent. We examined whether aerobic fitness moderated the effects of cannabis on cortical surface structure and whether gender may play a moderating role. Seventy-four adolescents and young adults completed three-weeks of monitored abstinence, aerobic fitness testing, and structural magnetic resonance imaging (sMRI). Whole-sample linear regressions examined the effects of gender, VO₂ max, cannabis use, and their interactions on the surface area (SA) and local gyrification index (LGI). Cannabis use was associated with greater cuneus SA. Gender-by-cannabis predicted precuneus and frontal SA, and precentral, supramarginal, and frontal LGI; female cannabis users demonstrated greater LGI, whereas male cannabis users demonstrated decreased LGI compared to non-users. Aerobic fitness was positively associated with various SA and LGI regions. Cannabis-by-aerobic fitness predicted cuneus SA and occipital LGI. These findings demonstrate that aerobic fitness moderates the impact of cannabis on cortical surface structure, and gender differences are evident. These moderating factors may help explain inconsistencies in the literature and warrant further investigation. Present findings and aerobic fitness literature jointly suggest aerobic intervention may be a low-cost avenue for improving cortical surface structure, although the impact may be gender-specific. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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13 pages, 933 KiB

Open AccessArticle

Frontal Alpha Asymmetry and Inhibitory Control among Individuals with Cannabis Use Disorders

by Alina Shevorykin, Lesia M. Ruglass and Robert D. Melara

Brain Sci. 2019, 9(9), 219; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9090219 - 29 Aug 2019

Cited by 7 | Viewed by 3508

Abstract

To better understand the biopsychosocial mechanisms associated with development and maintenance of cannabis use disorder (CUD), we examined frontal alpha asymmetry (FAA) as a measure of approach bias and inhibitory control in cannabis users versus healthy nonusers. We investigated: (1) whether FAA could distinguish cannabis users from healthy controls; (2) whether there are cue-specific FAA effects in cannabis users versus controls; and (3) the time course of cue-specific approach motivation and inhibitory control processes. EEG data were analyzed from forty participants (CUD (n = 20) and controls (n = 20)) who completed a modified visual attention task. Results showed controls exhibited greater relative right hemisphere activation (indicating avoidance/withdrawal motivation) when exposed to cannabis cues during the filtering task. By contrast, cannabis users exhibited greater relative left activation (approach) to all cues (cannabis, positive, negative, and neutral), reflecting a generalized approach motivational tendency, particularly during later stages of inhibitory control processes. The difference between cannabis users and controls in FAA was largest during mid- to late processing stages of all cues, indicating greater approach motivation during later stages of information processing among cannabis users. Findings suggest FAA may distinguish cannabis users from healthy controls and shows promise as a measure of inhibitory control processes in cannabis users. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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12 pages, 229 KiB

Open AccessArticle

Marijuana Use among African American Older Adults in Economically Challenged Areas of South Los Angeles

by Sharon Cobb, Mohsen Bazargan, James Smith, Homero E. del Pino, Kimberly Dorrah and Shervin Assari

Brain Sci. 2019, 9(7), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9070166 - 16 Jul 2019

Cited by 9 | Viewed by 4118

Abstract

Purpose: This study explored demographic, social, behavioral, and health factors associated with current marijuana use (MU) among African American older adults who were residing in economically challenged areas of south Los Angeles. Methods: This community-based study recruited a consecutive sample of African American older adults (n = 340), age ≥ 55 years, residing in economically challenged areas of South Los Angeles. Interviews were conducted to collect data. Demographics (age and gender), socioeconomic status (educational attainment, income, and financial strain), marital status, living alone, health behaviors (alcohol drinking and cigarette smoking), health status (number of chronic medical conditions, body mass index, depression, and chronic pain), and current MU were collected. Logistic regression was used to analyze the data. Results: Thirty (9.1%) participants reported current MU. Age, educational attainment, chronic medical conditions, and obesity were negatively associated with current MU. Gender, income, financial strain, living alone, marital status, smoking cigarettes, drinking alcohol, depression, and pain did not correlate with MU. Conclusion: Current MU is more common in younger, healthier, less obese, less educated African American older adults. It does not seem that African American older adults use marijuana for the self-medication of chronic disease, pain, or depression. For African American older adults, MU also does not co-occur with cigarette smoking and alcohol drinking. These results may help clinicians who provide services for older African Americans in economically challenged urban areas. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

17 pages, 732 KiB

Open AccessArticle

Descriptive Psychopathology of the Acute Effects of Intravenous Delta-9-Tetrahydrocannabinol Administration in Humans

by Marco Colizzi, Nathalie Weltens, Philip McGuire, Lukas Van Oudenhove and Sagnik Bhattacharyya

Brain Sci. 2019, 9(4), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9040093 - 25 Apr 2019

Cited by 17 | Viewed by 4368

Abstract

Background: Cannabis use can increase the risk of psychosis, and the acute administration of its key psychoactive ingredient, delta-9-tetrahydrocannabinol (∆9-THC), can induce transient psychotomimetic symptoms. Methods: A double-blind, randomized, placebo-controlled crossover design was used to investigate the symptomatic effects of acute intravenous administration of ∆9-THC (1.19 mg/2 mL) in 16 healthy participants (seven males) with modest previous cannabis exposure. Results: In the 20 min following acute ∆9-THC administration, symptomatic effects of at least mild severity were present in 94% of the cohort, with moderate to severe symptoms having a much lower prevalence (19%). Nearly one-third (31%) of the volunteers were still experiencing protracted mild symptomatic effects 2.5 h after exposure to ∆9-THC. Compared to the Δ9-THC challenge, most of the study participants did not experience any symptomatic effects following placebo administration (62%). Acute physical reactions were 2.5 times more frequent after Δ9-THC (31%) than placebo (12%). Male and female participants differed in terms of acute Δ9-THC effects, with some negative symptoms occurring more frequently in female (56% to 89%) than male participants (0% to 29%), and acute physical reactions occurring exclusively in the female gender (56%). Conclusions: These results have implications for future research, also in light of cannabis being the most widely used illicit drug. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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Review

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32 pages, 511 KiB

Open AccessReview

A Systematic Review of Human Neuroimaging Evidence of Memory-Related Functional Alterations Associated with Cannabis Use Complemented with Preclinical and Human Evidence of Memory Performance Alterations

by Grace Blest-Hopley, Vincent Giampietro and Sagnik Bhattacharyya

Brain Sci. 2020, 10(2), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020102 - 13 Feb 2020

Cited by 19 | Viewed by 5120

Abstract

Cannabis has been associated with deficits in memory performance. However, the neural correlates that may underpin impairments remain unclear. We carried out a systematic review of functional magnetic resonance imaging (fMRI) studies investigating brain functional alterations in cannabis users (CU) compared to nonusing controls while performing memory tasks, complemented with focused narrative reviews of relevant preclinical and human studies. Twelve studies employing fMRI were identified finding functional brain activation during memory tasks altered in CU. Memory performance studies showed CU performed worse particularly during verbal memory tasks. Longitudinal studies suggest that cannabis use may have a causal role in memory deficits. Preclinical studies have not provided conclusive evidence of memory deficits following cannabinoid exposure, although they have shown evidence of cannabinoid-induced structural and histological alteration. Memory performance deficits may be related to cannabis use, with lower performance possibly underpinned by altered functional activation. Memory impairments may be associated with the level of cannabis exposure and use of cannabis during developmentally sensitive periods, with possible improvement following cessation of cannabis use. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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17 pages, 582 KiB

Open AccessReview

Factors Moderating the Association between Cannabis Use and Psychosis Risk: A Systematic Review

by Sanne J. van der Steur, Albert Batalla and Matthijs G. Bossong

Brain Sci. 2020, 10(2), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020097 - 12 Feb 2020

Cited by 45 | Viewed by 8895

Abstract

Increasing evidence indicates a relationship between cannabis use and psychosis risk. Specific factors, such as determinants of cannabis use or the genetic profile of cannabis users, appear to moderate this association. The present systematic review presents a detailed and up-to-date literature overview on factors that influence the relationship between cannabis use and psychosis risk. A systematic search was performed according to the PRISMA guidelines in MEDLINE and Embase, and 56 studies were included. The results show that, in particular, frequent cannabis use, especially daily use, and the consumption of high-potency cannabis are associated with a higher risk of developing psychosis. Moreover, several genotypes moderate the impact of cannabis use on psychosis risk, particularly those involved in the dopamine function, such as AKT1. Finally, cannabis use is associated with an earlier psychosis onset and increased risk of transition in individuals at a clinical high risk of psychosis. These findings indicate that changing cannabis use behavior could be a harm reduction strategy employed to lower the risk of developing psychosis. Future research should aim to further develop specific biomarkers and genetic profiles for psychosis, thereby contributing to the identification of individuals at the highest risk of developing a psychotic disorder. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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Other

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9 pages, 452 KiB

Open AccessPerspective

The Endocannabinoid System as a Potential Mechanism through which Exercise Influences Episodic Memory Function

by Paul D. Loprinzi, Liye Zou and Hong Li

Brain Sci. 2019, 9(5), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9050112 - 16 May 2019

Cited by 13 | Viewed by 5796

Abstract

Emerging research demonstrates that exercise, including both acute and chronic exercise, may influence episodic memory function. To date, mechanistic explanations of this effect are often attributed to alterations in long-term potentiation, neurotrophic production, angiogenesis, and neurogenesis. Herein, we discuss a complementary mechanistic model, suggesting that the endocannabinoid system may, in part, influence the effects of exercise on memory function. We discuss the role of the endocannabinoid system on memory function as well as the effects of exercise on endocannabinoid alterations. This is an exciting line of inquiry that should help delineate new insights into the mechanistic role of exercise on memory function. Full article

(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)

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