Increasingly potent concentrated cannabis products containing high levels of Δ9-tetrahydrocannabinol (THC) are being consumed with alcohol. This combination is known to acutely impair cognitive and psychomotor abilities, although few studies have evaluated alcohol and cannabis co-use using neural measures. This naturalistic feasibility study explored the acute effects of co-intoxication on...
Polysubstance use of opioids and stimulants is increasingly common among individuals with a substance use disorder, yet most researchers examine these substances in isolation. This gap limits our understanding of the effects of polysubstance use and how these differ from single substance use. Here, we examined the impact of single versus polysubstance exposure of fentanyl and methamphetamine on...
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on...
Cue-induced craving-the desire to use a drug triggered by exposure to cues associated with prior use-is a central mechanism in the development and maintenance of problematic substance use behaviours. Drug cues have the power to induce craving even in long-term abstinent individuals, which has led clinicians to advise patients to avoid the people, places and objects that are associated with...
Ketamine abuse damages brain function and structure, increasing reactive oxygen species and apoptosis in the cerebral cortex, but moderate-intensity continuous training (MICT) can enhance antioxidant defences and reduce apoptosis. Therefore, we aimed to answer whether MICT can reduce the side effects of chronic ketamine abuse. 24 Wistar rats were split into control (CON), ketamine abuse (KET),...
Despite its widespread use and popularity, cannabis is known to impact higher order cognitive processes such as attention and executive function. However, far less is known about the impact of chronic cannabis use on cognitive flexibility, a component of executive function, and this is especially true for the underlying functional connectivity dynamics. To address this, we enrolled 25 chronic...
Abstract Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic‐assisted therapy with psilocybin and lysergic acid...
Drugs of abuse induce cell type-specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) that can bias signalling towards D1-MSNs and enhance relapse vulnerability. Whether Δ9 -tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to...
Abstract Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5‐HT 2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This...
agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals,...
2-Fluorodeschloroketamine (2-FDCK) as a substitute for ketamine has emerged among drug abusers in recent years. However, 2-FDCK has not been controlled or regulated in many countries, which may be partly related to the lack of evidence on its abuse potential. In this study, we evaluated the abuse potential of 2-FDCK via the tests of the conditioned place preference (CPP), locomotor...
Social norms and legality surrounding the use of medical and recreational cannabis are changing rapidly. The prevalence of cannabis use in adolescence is increasing. The aim of this study was to assess any sex-based neurobiological effects of chronically inhaled, vaporised cannabis on adolescent female and male mice. Female and male mice were exposed daily to vaporised cannabis (10.3%...
The resurgence of interest in using psychedelic drugs, including lysergic acid diethylamide (LSD), in psychiatry has drawn attention to the medically unsupervised practice of 'microdosing'. Thousands of users claim that very low doses of LSD, taken at 3-4-day intervals, improve mood and cognitive function., However, few controlled studies have described the effects of the drug when taken in...
Using a federally compatible, naturalistic at-home administration procedure, the present study examined the acute effects of three cannabis flower chemovars with different tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios, in order to test whether chemovars with a higher CBD content produce different effects. Participants were randomly assigned to ad libitum administration of one of three...
Some evidence suggests that males and females may differ in their responses to acute cannabis effects, including subjective drug effects and behavioural effects, and cannabinoid pharmacokinetics. This is significant given current changes to cannabis-related policies and, in consequence, increased cannabis accessibility. The present study combines data from two randomized controlled trials to...
Heavy cannabis use (HCU) is frequently associated with a plethora of cognitive, psychopathological and sensorimotor phenomena. Although HCU is frequent, specific patterns of abnormal brain structure and function underlying HCU in individuals presenting without cannabis-use disorder or other current and life-time major mental disorders are unclear at present. This multimodal magnetic resonance...
Abstract: Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4‐F‐PCP and 4‐Keto‐PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4‐F‐PCP...
Abstract Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self‐stimulation (ICSS) (oICSS) to re‐examine the abuse potential of cannabinoids in mice. A specific adeno‐associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA)...
Abstract An increasing number of N ‐2‐methoxybenzyl‐phenethylamine (NBOMe) derivatives are being misused worldwide, including the potent hallucinogen 2‐(4‐bromo‐2,5‐dimethoxyphenyl)‐ N ‐(2‐methoxybenzyl)ethanamine (25B‐NBOMe). However, the number of studies characterizing the abuse potential and psychopharmacological properties of 25B‐NBOMe is limited; thus, we examined its rewarding and...
Addiction BiologyNovember 2020Daniela Neuhofer, Sade M Spencer, Vivian C Chioma et al.
Glutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self-administration. We used intravenous self-administration of two constituents of...
AbstractRepeated exposure to drugs produces a plethora of persistent brain changes, some of which underlie the development of drug addiction. An important objective of addiction research is to identify the brain changes that might mediate the transition from drug use to drug misuse. The persistent accumulation of the transcription factor, ∆FosB, following repeated drug exposure provides a means...
The relative value of and motivation for abused drugs often increases with drug experience and differs based on drug availability. Here, we determined how different intake patterns of fentanyl, a μ‐opioid agonist, alter economic demand for fentanyl and how 5‐HT2A receptor stimulation affects economic demand for fentanyl. We used a within‐session demand threshold procedure to characterize...
Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory-entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was to investigate naphyrone's pharmacokinetics,...
Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug....
Addiction BiologyNovember 2019Christina S Meade, Ryan P Bell, Sheri L Towe et al.
Marijuana use, which is disproportionately prevalent among human immunodeficiency virus (HIV)-infected persons, can alter activity in fronto-parietal regions during cognitively demanding tasks. While HIV is also associated with altered neural activation, it is not known how marijuana may further affect brain function in this population. Our study examined the independent and additive effects of...