Bernard Le Foll

Bernard Le Foll
Centre for Addiction and Mental Health · Translational Addiction Research Laboratory

About

540
Publications
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Publications

Publications (540)
Article
Introduction: Patient satisfaction is a critical measure of quality of care across health disciplines because it may affect clinical outcomes. Objectives: This study aimed to examine longitudinal patient satisfaction in individuals with opioid use disorder (OUD) randomized to receive either standard methadone or flexible buprenorphine/naloxone m...
Article
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Background The dual COVID-19 and overdose emergencies amplified strain on healthcare systems tasked with responding to both. One downstream consequence of the pandemic in the USA and Canada was a surge in drug overdoses resulting from public health-restricted access to services and an increasingly toxic unregulated drug supply. This study aimed to...
Article
Gamma-aminobutyric acid (GABA) signaling plays a crucial role in drug reward and the development of addiction. Historically, GABA neurochemistry in humans has been difficult to study due to methodological limitations. In recent years, proton magnetic resonance spectroscopy (1H-MRS, MRS) has emerged as a non-invasive imaging technique that can detec...
Chapter
Substance use disorders are a leading cause of morbidity and mortality, and available pharmacological treatments are of modest efficacy. Histamine is a biogenic amine with four types of receptors. The histamine H3 receptor (H3R) is an autoreceptor and also an heteroreceptor. H3Rs are highly expressed in the basal ganglia, hippocampus and cortex, an...
Article
Objective: Extensive exposure to prescription-type opioids has resulted in major harm worldwide, calling for better-adapted approaches to opioid agonist therapy. The authors aimed to determine whether flexible take-home buprenorphine/naloxone is as effective as supervised methadone in reducing opioid use in prescription-type opioid consumers with...
Article
Background and aims: Fentanyl is primarily responsible for the current phase of the overdose epidemic in North America. Despite the benefits of treatment with medications for opioid use disorder (MOUD), there are limited data on the association between fentanyl, MOUD type and treatment engagement. The objectives of this analysis were to measure th...
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Rationale With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. Objectives The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance,...
Article
Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19–29 years with recent history of binge drinking completed this w...
Article
(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (1H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, Psy...
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Introduction With the increasing number of cannabis users and more jurisdictions allowing medical cannabis, more evidence-based knowledge about the prevalence of cannabis use disorder (CUD) among medical users is greatly needed. Objectives To examine and compare the prevalence and severity of CUD and the prevalence of different CUD criteria among...
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Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (20...
Chapter
Before 1990, the multiplicity of dopamine receptors beyond D1 and D2 had remained a controversial concept, despite its substantial clinical implications, at a time when it was widely accepted that dopamine interacted with only two receptor subtypes, termed D1 and D2, differing one from the other by their pharmacological specificity and opposite eff...
Article
Tobacco smoking is a major determinant of preventable morbidity and mortality worldwide. More than a billion people smoke, and without major increases in cessation, at least half will die prematurely from tobacco-related complications. In addition, people who smoke have a significant reduction in their quality of life. Neurobiological findings have...
Article
Background Traditional randomized controlled trials have demonstrated the efficacy of pharmacotherapy for smoking cessation. However, accessibility to treatments remains a barrier, necessitating the remote delivery of evidence-based cessation interventions. The aim of this study was to evaluate the effectiveness of an online treatment that included...
Article
Alcohol and cannabis are the two most commonly found intoxicating substances in fatally injured drivers. Epidemiological studies have demonstrated that the use of alcohol or cannabis can lead to an increase in the risk of a motor vehicle collision. Reducing the risks associated with driving under the influence of alcohol or cannabis is achieved par...
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The mu-opioid receptor (MOR) mediates the rewarding properties of many psychoactive drugs and is an important target in the treatment of addictions. Functional interactions between the opioid and endocannabinoid systems are established and have been hypothesized to contribute to the effects of cannabis. We investigated associations between three si...
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Polysubstance use is a growing public health concern that has been associated with poor clinical outcomes. Compared to single-drug users, this population suffers greater deficits in cognitive function, which hinder treatment success and recovery. Despite its high prevalence and poor prognosis, epidemiological research on polysubstance use and accom...
Article
Objective: Post-traumatic stress disorder (PTSD) is a common risk factor for opioid use disorder (OUD). However, not all individuals with PTSD develop OUD when exposed to opioids. As the underlying moderators remain unexplored, this analysis aimed to determine if non-traumatic adverse experiences and stressors prior to the age of 18 moderate the re...
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Major depressive disorder (MDD) and alcohol use disorder (AUD) are leading causes of disability, and patients are frequently affected by both conditions. This comorbidity is known to confer worse outcomes and greater illness severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method that has demonstrated...
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The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis and may affect hunger, caloric intake, and nutrient absorption. Obesity has been associated with higher levels of the endogenous cannabinoid transmitters (endocannabinoids). Therefore, the ECS is an important target in obesity treatment. Modulating the enzy...
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Background Randomized trials of complex interventions are increasingly including qualitative components to further understand factors that contribute to their success. In this paper, we explore the experiences of health care practitioners in a province wide smoking cessation program (the Smoking Treatment for Ontario Patients program) who participa...
Article
Background: It is evident that an association between smoking and post-traumatic stress disorder (PTSD) exists, but research is lacking in establishing the directionality of the relationship. Methods: We used longitudinal data from wave I (2001-2002) and II (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESAR...
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Background Adequate opioid prescribing is critical for therapeutic success of pain management. Despite the widespread use of opioids, optimized opioid therapy remains unresolved with risk of accidental lethal overdosing. With the emergence of accumulating evidence linking genetic variation to opioid response, pharmacogenetic based treatment recomme...
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Social anxiety disorder (SAD) is a highly prevalent psychiatric disorder that presents with an early age of onset, chronic disease course, and increased risk of psychiatric comorbidity. Current treatment options for SAD are associated with low response rates, suboptimal efficacy, and possible risk of adverse effects. Investigation of new neurobiolo...
Article
Background: Cannabis is one of the drugs most often found in drivers involved in serious motor vehicle collisions. Validity and reliability of roadside cannabis detection strategies are questioned. This pilot study aimed to investigate the relationship between eye characteristics and cannabis effects in simulated driving to inform potential develop...
Article
Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD). In animals, voluntary alcohol consumption increases DRD3 expression, and pharmacological blockade of DRD3s attenuates alcohol self-administration and reinstatement of alcohol seeking. However, these findings have yet to be translated in hum...
Article
Objective: This study aimed to estimate the survival probabilities related to the occurrence of major depressive episodes (MDEs) after the onset of substance use disorders (SUDs) using data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III. Methods: The Alcohol Use Disorder and Associated Disabilities Interview...
Article
A recent study of the impact of smoked cannabis on simulated driver behavior demonstrated a reduction in mean speed after smoked cannabis. Previous research identified an association between personality and individual differences and acute drug effects. The present study examined the impact of personality on the reduction in mean speed after smokin...
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As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for ass...
Article
Background and Objective The introduction of cannabis as a legalized recreational drug in Canada has led to significant changes in public health policy. Tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis and its absorption, distribution, metabolism, and elimination are poorly understood. The use of THC can impair an individ...
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Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [ ¹¹ C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes i...
Article
Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young a...
Article
Introduction Variation in CYP2A6, the primary enzyme responsible for nicotine metabolism, is associated with nicotine dependence, cigarette consumption, and abstinence outcomes in smokers. The impact of CYP2A6 activity on nicotine reinforcement and tobacco cue-reactivity, mechanisms that may contribute to these previous associations, has not been f...
Article
Objectives: Following recommendations from the Lower Risk Cannabis Use Guidelines, we evaluated how lower risk cannabis use (late initiation and low use frequency) was associated with the risk of developing cannabis abuse/dependence over a 3-year follow-up period compared to 12-month abstinence (controls) or higher risk cannabis use (early initiat...
Article
Relapse is common amongst smokers attempting to quit and tobacco cue-induced craving is an important relapse mechanism. Preclinical studies commonly use cue-induced reinstatement of nicotine seeking to investigate relapse neurobiology. Previous research suggests dependence severity and nicotine intake history affect smoking resumption and cue-induc...
Preprint
Full-text available
Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in...
Article
Full-text available
Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored t...
Article
Background Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether thi...
Chapter
Substance use disorders are prevalent and severe conditions associated with numerous health, social, and economic harms. While the neurobiological mechanisms are still not fully understood, adaptations in multiple neurotransmitter systems have been implicated in the development and maintenance of substance use disorders. The advent of molecular ima...
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Aims Opioid misuse and overuse has contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five‐step modified Delphi process, we aimed to develop consensus‐based recommendations on: 1) when and how to safely initiate and titrate cannab...
Article
In many countries, liberalisation of the legislation regulating the use of cannabis has outpaced rigorous scientific studies, and a growing number of patients presenting for surgery consume cannabis regularly. Research to date suggests that cannabis can impact perioperative outcomes. We present recommendations obtained using a modified Delphi metho...
Article
: In the last 2 decades, there is a renaissance in the scientific investigation of the therapeutic potential of psychedelic compounds. It is studied for the treatment of many psychiatric disorders, including posttraumatic stress disorder. The treatment is always done in the setting of psychedelic-assisted psychotherapy. A little is known about the...
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Legalization and commercial sale of non-medical cannabis has led to increasing diversity and potency of cannabis products. Some of the American states that were the first to legalize have seen rises in acute harms associated with cannabis use, e.g. Colorado has seen increases in emergency department visits for cannabis-related acute psychological d...
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Background: Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive; as such, there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy are not effective for many smokers,...
Article
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A high percentage of subjects diagnosed with alcohol use disorder (AUD) suffer from sleeping difficulties. Lack of sleep could lead AUD patients to relapse or, sometimes, to suicide. Most of the currently prescribed medications to treat this complex problem retain a high risk of side effects and/or dependence. Therefore, the aim of the current clin...
Article
Introduction: Tobacco use disorder (TUD) is a chronic relapsing condition. Existing pharmacotherapy can assist smokers to initiate smoking cessation, but relapse rates remain high. Novel therapeutics are required to help people quit and also to prevent relapse. The endocannabinoid system has been increasingly implicated in reward and addiction proc...
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Targeting peroxisome proliferator-activated receptors (PPARs) has received increasing interest as a potential strategy to treat substance use disorders due to the localization of PPARs in addiction-related brain regions and the ability of PPAR ligands to modulate dopamine neurotransmission. Robust evidence from animal models suggests that agonists...
Article
Objectives To examine acute and residual mood and cognitive performance in young adult regular cannabis users following smoked cannabis. Methods Ninety-one healthy young adults completed this double-blind, placebo-controlled, parallel-groups study. Participants were randomized to receive active (12.5% THC) or placebo cannabis with a 2:1 allocation...
Article
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Background: Although medical cannabis has been available to Canadians since 2001, there is little research on the effects of cannabis on driving in individuals who use cannabis medically. This pilot study sought to determine the effects of therapeutic cannabis use on simulated driving. Methods: Eligible participants reported daily use of cannabis f...
Article
Background and purpose: BF2.649 (pitolisant, Wakix®) is a novel histamine H3 receptor (H3R) inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo H3R occupancy of BF2.649 using positron emission tomography (PET) brain imaging with the H3R antagonist radioligand...
Article
There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinic...
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Full-text available
Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship betwee...
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Full-text available
Rationale Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ⁹-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men. Objectives The objective of this secondary analysis was to examine sex...
Article
Background: Smoking prevalence among those with alcohol dependence is much higher than the general population. Despite this, cessation treatment in those with concurrent alcohol dependence is seldom undertaken. We conducted a randomized, placebo-controlled, double-blind pilot study, whereby patients enrolled at an addiction treatment facility in d...
Article
Full-text available
The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whet...
Article
Background: There is inconsistent evidence in the literature as to whether or not Alcohol Use Disorder (AUD) is a risk factor for Post-Traumatic Stress Disorder (PTSD). Objectives: We evaluated the risk of developing PTSD after trauma exposure in individuals with AUD. As a secondary analysis, we also tested if alcohol dependence or alcohol abuse se...
Article
The endocannabinoid and dopaminergic systems have independently been implicated in substance use disorder and obesity. We investigated a potential interaction between genetically inherited variation in fatty acid amide hydrolase (FAAH, C385A), which metabolizes the cannabis-like endocannabinoid anandamide, and dopaminergic system, measured by dopam...
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The insular cortex has been linked to a multitude of functions. In contrast, the nearby claustrum is a densely connected subcortical region with unclear function. To view the insula-claustrum region from the molecular perspective we analyzed the transcriptomic profile of these areas in six adult and four fetal human brains. We identified marker gen...
Article
Dopamine, a neurotransmitter with 5 receptor subtypes, is critical to the dependence-forming properties of drugs of abuse. The role of the dopamine D4 receptor subtype in substance use disorders has remained somewhat elusive but the recent development of selective ligands holds promise for future investigations of this receptor subtype in substance...
Preprint
Background Randomized trials of complex interventions are increasingly including qualitative components to further understand factors that contribute to the success of complex interventions. In this paper, we explore the experiences of health care professionals who participated in the COMBAT trial; a web-based intervention implemented in the Ontari...
Article
Background: Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users. Methods: In this double-blind, placebo-controlled, parallel-...
Article
Full-text available
Background: Clinical decision support systems (CDSSs) may promote practitioner adherence to evidence-based guidelines. This study examined if the addition of a CDSS influenced practitioner delivery of a brief intervention with treatment-seeking smokers who were drinking above recommended alcohol consumption guidelines, compared with practitioners...
Chapter
Tobacco kills every year approximately six million people as a direct result of direct use, and it is still considered one of the most excruciating threats for human health worldwide. The low successful rates of the currently available pharmacotherapies to assist in quitting tobacco use suggest there is a need for more effective treatments.The intr...
Chapter
Despite a number of approved medications for alcohol use disorder (AUD), this chronic relapsing disease still produces a considerable global burden, with both health-related and financial consequences. While clinical trials are a critical step in drug development, human laboratory studies provide the field with means of screening pharmacotherapy fo...
Chapter
Every year, billions of dollars are spent treating smoking and related conditions, yet smoking-related morbidity and mortality continue to rise. There are currently only three FDA-approved medications for smoking cessation: nicotine replacement therapy, bupropion, and varenicline. Although these medications increase abstinence rates, most individua...
Article
Full-text available
Substance use disorders (SUDs) are a growing public health concern with only a limited number of approved treatments. However, even approved treatments are subject to limited efficacy with high long-term relapse rates. Current treatment approaches are typically a combination of pharmacotherapies and behavioral counselling. Growing evidence and tech...