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  • ∆9-tetrahydrocannabinol (THC)
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Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Abstract Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of...
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Pharmacokinetic, behavioral, and brain activity effects of Δ9-tetrahydrocannabinol in adolescent male and female rats

Abstract Δ9-tetrahydrocannabinol (THC) is the intoxicating constituent of cannabis and is responsible for the drug’s reinforcing effects. Retrospective human studies suggest that cannabis use during adolescence is linked to long-term negative psychological outcomes, but in such studies it is difficult to distinguish the effects of THC from those of coexisting factors. Therefore, translationally relevant animal models are required to properly investigate THC effects in adolescents. However, though the relevance of these studies depends upon human-relevant dosing, surprisingly little is known about THC pharmacology and its effects on behavior and brain activity in adolescent rodents—especially in females. Here, we conducted a systematic investigation of THC...
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Do Cannabis Users Reduce Their THC Dosages When Using More Potent Cannabis Products? A Review

Abstract Background: Higher potency cannabis products are associated with higher risks of negative physical and psychological outcomes. The US cannabis industry has opposed any restrictions on THC levels, arguing that people titrate their THC doses when consuming higher potency products. Objective: To review research on the degree to which people who use cannabis for recreational purposes can and do titrate their THC doses. Method: A systematic search was conducted for studies published from 1973 to 2020. We included (1) experimental laboratory studies on dose titration of cannabis products that varied in THC content; (2) observational studies on the use of more potent products; and...
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Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

Abstract Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently...
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Determining the magnitude and duration of acute Δ9-tetrahydrocannabinol (Δ9-THC)-induced driving and cognitive impairment: A systematic and meta-analytic review

Abstract The increasing legal availability of cannabis has important implications for road safety. This systematic review characterised the acute effects of Δ9-THC on driving performance and driving-related cognitive skills, with a particular focus on the duration of Δ9-THC-induced impairment. Eighty publications and 1534 outcomes were reviewed. Several measures of driving performance and driving-related cognitive skills (e.g. lateral control, tracking, divided attention) demonstrated impairment in meta-analyses of “peak” Δ9-THC effects (p’s<0.05). Multiple meta-regression analyses further found that regular cannabis users experianced less impairment than ‘other’ (mostly occasional) cannabis users (p = 0.003) and that the magnitude of oral (n = 243 effect estimates [EE]) and inhaled (n = 481 EEs) Δ9-THC-induced...
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A review on the syntheses of Dronabinol and Epidiolex as classical cannabinoids with various biological activities including those against SARS-COV2

Abstract The very important psychoactive phytocannabinoid from Cannabis Δ9 tetrahydrocannabinol (Δ9-THC) and its non-psychotropic member is cannabidiol (CBD). These compounds have a variety of pharmacological activities. THC has been approved for the treatment of nausea caused by chemotherapy, multiple sclerosis and chronic and neuropathic pain and research is underway to use it to treat stimulation of dementia, anorexia nervous and Tourette’s syndrome. CBD has therapeutic benefits in Epilepsy, neuroprotective, cancer, inflammatory and anxiety. Recognizing candidate drugs efficiently in the new SARS-CoV2 disease 2019 (Covid-19) is crucial. Cannabidiol and Δ9-tetrahydrocannabinol have immunomodulatory and anti-inflammatory effects. They can reduce the uncontrolled cytokine production of acute lung...
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Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats

Please use this link to access this publication. Abstract With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring...
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Effect of Δ9-Tetrahydrocannabinol on frontostriatal resting state functional connectivity and subjective euphoric response in healthy young adults

Please use this link to access this publication. Abstract Background Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis use. Methods Participants received THC (n = 24) or placebo (n = 22) in a double-blind, randomized, between-subject design. Participants completed self-report measures of euphoria and drug-liking throughout the visit. Approximately 120 min after drug administration, participants completed an 8-min resting state functional MRI (rs-fMRI) scan. We utilized seed-based connectivity of...
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Appetitive, antinociceptive, and hypothermic effects of vaped and injected Δ-9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex

Please use this link to access this publication. Abstract Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N = 22, 5–6/sex per group) received THC via...
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The Yin and Yang of Cannabis: A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ9-Tetrahydrocannabinol and Cannabidiol

Please use this link to access this publication. Abstract Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been the most investigated cannabinoids at the human and preclinical levels, although the neurobiological mechanisms underlying their effects remain unclear. Human experimental evidence complemented by observational studies suggests that THC may have psychotogenic effects while CBD may have antipsychotic effects. However, whether their effects on brain function are consistent with their opposing behavioral effects remains unclear. To address this, here we synthesize neuroimaging evidence investigating the acute effects of THC and CBD on human brain function using a range of neuroimaging techniques, with an aim to identify the key...
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