Chronic Cannabis Research Articles

The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls

BackgroundPreclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults.MethodsAs part of the ‘CannTeen’ project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16–17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26–29-year-olds) and adult controls (n = 64). Users used cannabis 1–7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively.ResultsUsers had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition.ConclusionsConsistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

P29. Verbal Episodic Memory, Spatial Working Memory, and Response Inhibition in Adolescent and Adult Cannabis Users and Controls

Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults.

P9. Computational Mechanisms Underlying Drug-Based Decision Making and Momentary Craving in Chronic Cannabis Users

Craving is a core feature and a key target of investigation in understanding addiction. However, to date, the computational mechanisms underlying craving remain largely unknown. In this study, we developed a novel computational approach to test the hypothesis that momentary drug craving arises from discrepancies between expected and received drug rewards, i.e., drug-related prediction error (PE).

Cannabis Use and Neuroadaptation: A Call for Δ 9 -Tetrahydrocannabinol Challenge Studies.

Currently, the assessment of the neurobehavioral consequences of repeated cannabis use is restricted to studies in which brain function of chronic cannabis users is compared to that of non-cannabis using controls. The assumption of such studies is that changes in brain function of chronic users are caused by repeated and prolonged exposure to acute cannabis intoxication. However, differences in brain function between chronic cannabis users and non-users might also arise from confounding factors such as polydrug use, alcohol use, withdrawal, economic status, or lifestyle conditions. We propose a methodology that highlights the relevance of acute Δ9-tetrahydrocannabinol (THC) dosing studies for a direct assessment of neuroadaptations in chronic cannabis users. The approach includes quantification of neurochemical, receptor, and functional brain network changes in response to an acute cannabis challenge, as well as stratification of cannabis using groups ranging from occasional to cannabis-dependent individuals. The methodology allows for an evaluation of THC induced neuroadaptive and neurocognitive changes across cannabis use history, that can inform neurobiological models on reward driven, compulsive cannabis use.

The Neurotoxic Effects of Cannabis on Brain: Review of Clinical and Experimental Data

Cannabis is the most widely used illicit drug worldwide. Evidence indicated negative impact for cannabis on the brain. Animal research and in vitro studies using delta-9-THC (THC) or cannabis extracts with high THC content provided evidence for a detrimental effect on neuronal integrity with DNA damage, cell shrinkage, atrophy and apoptosis. The mechanisms by which herbal cannabis affects brain structure and function are not clear but impaired mitochondrial functioning, reduced glucose availability and inhibition of brain energetic metabolism by cannabis have been shown. Clinical studies investigating the effects of cannabis in humans found raised serum levels of proinflammatory cytokines in chronic cannabis users. Human studies also indicated increased oxidative stress biomarkers and reduced antioxidants in blood of chronic cannabis users. Preclinical data on the effect of cannabis or THC on oxidative stress, however, were less conclusive in that cannabis might increase or attenuate oxidative stress and neurotoxicity. The aim of this review is to summarize the evidence from animal and clinical studies pertaining to the toxic effects of cannabis and its main psychoactive ingredient THC on the brain and possible mechanisms involved.

Arrhythmic Effects of Cannabis in Ischemic Heart Disease.

Rationale: Cannabis use is increasing worldwide, especially among older individuals at risk for chronic ischemic heart disease (IHD). However, little is known about the arrhythmic effects of cannabis use in IHD. Accordingly, we prospectively assessed the relationship between cannabis use, heart rate (HR), and arrhythmias in healthy age-matched controls and subjects with IHD. Methods: Healthy controls (n=37, 57% men) and subjects with IHD (myocardial infarction ≥3 months ago; n=24, 58% men) who used cannabis wore a Zio® (iRhythm Technologies) monitor for 14 days. Noncannabis using ischemic subjects (n=35, 51% males) wore Zio monitors for standard clinical indications. Baseline HR was compared with average HR measured for 4 h following consumption and changes in HR and frequency of arrhythmias were correlated with cannabis use. Results: In controls, HR increased 20 min (4.99±6.7 bpm, p=0.08) after use, then declined 4 h following use (-7.4±7.7, p<0.001). Conversely, subjects with IHD showed minimal HR increase (1.6±3.9 bpm) and blunted HR decline (-3.4±5.6 bpm, p<0.001). Supraventricular tachycardia (SVT) (29.7% vs. 58.3%; p=0.04) and nonsustained ventricular tachycardia (NSVT) (5.6% vs. 47.8%, p=0.01) were the most frequently occurring arrhythmias in controls and IHD subjects, respectively. Incidence of SVT decreased as cannabis use increased in both groups. Conversely, NSVT tended to increase with increased use in controls, and was significantly more prevalent in IHD. However, overall arrhythmia burden did not differ between cannabis users and nonusers with IHD. Conclusion: Our findings demonstrate that chronic cannabis use is associated with only mild HR changes, which are blunted in IHD. In addition, our data suggest that among cannabis users, arrhythmias are more frequent in IHD subjects that in healthy subjects.

Examining Inhibitory Affective Processing Within the Rostral Anterior Cingulate Cortex Among Abstinent Cannabis-Using Adolescents and Young Adults.

Cannabis use has been associated with deficits in self-regulation, including inhibitory control. Cannabis users have previously exhibited both structural and functional deficits in the rostral anterior cingulate cortex (rACC), a region involved in self-regulation of emotional response and inhibitory control. The present study aimed to examine whether abstinent cannabis users demonstrated abnormal functional activation and connectivity of the bilateral rACC during an emotional inhibitory processing task, and whether gender moderated these relationships. Cannabis-using (N = 34) and non-using (N = 32) participants ages 16–25 underwent at least 2-weeks of monitored substance use abstinence (excluding tobacco) and fMRI scanning while completing a Go/No-go task using fearful and calm emotional faces as non-targets. Multiple linear regression and ANCOVA were used to determine if cannabis group status was related to rACC activation and context-dependent functional connectivity, and whether gender moderated these relationships. Results showed decreased bilateral rACC activation in cannabis users during fearful response inhibition, although groups did not show any context-dependent connectivity differences between the left or right rACC during calm or fearful inhibition. Gender findings revealed that cannabis-using females compared to males did show aberrant connectivity between the right rACC and right cerebellum. These results are consistent with literature demonstrating aberrant structural and functional rACC findings and suggest that chronic cannabis use may disrupt typical rACC development—even after abstinence—potentially conferring risk for later development of mood disorders. Marginal gender-specific connectivity findings bolster continued findings regarding female vulnerability to effects of cannabis on cognition and affect. Findings should be assessed in longitudinal studies to determine causality and timing effects.

An atypical case of cicatricial pemphigoid vegetans in a young male and a review of the literature

Mucous membrane pemphigoid (MMP), previously known as cicatricial pemphigoid, is the second most frequent autoimmune subepithelial blistering disorder after bullous pemphigoid (BP). MMP has a broad spectrum of both clinical and immunological features, mostly affecting the mucous membranes, mainly the oral and ocular mucosae, but around 30% of cases develop skin lesions, which heal leaving atrophic scars and milia. Herein, we report a patient with widespread vegetating cutaneous and oral plaques, oral erosions, scarring conjunctivitis, and extensive mucosal lesions, who met the immunologic and microscopic criteria of cicatricial pemphigoid vegetans (CPV). The vegetative form of MMP is a very rare entity and, to our knowledge, this is the fifth patient recorded in the global literature. We present the unusual case of a young male who developed CPV possibly caused by chronic and heavy cannabis use and who was treated effectively with rituximab.

Effects of regular cannabis and nicotine use on acute stress responses: chronic nicotine, but not cannabis use, is associated with blunted adrenocortical and cardiovascular responses to stress.

Cannabis is one of the most prevalent substances used by tobacco smokers and, in light of the growing list of states and territories legalizing cannabis, it is expected that co-use of cannabis and nicotine will escalate significantly and will lead to continuing challenges with tobacco use. This study was conducted to examine the interactive effects of chronic cannabis and nicotine use on adrenocortical, cardiovascular, and psychological responses to stress and to explore sex differences in these effects. Participants (N = 231) included cannabis-only users, nicotine-only users, co-users of both substances, and a non/light-user comparison group. After attending a medical screening session, participants completed a laboratory stress session during which they completed measures of subjective states, cardiovascular responses, and salivary cortisol during baseline (rest) and after exposure to acute stress challenges. Nicotine use, but not cannabis use, was associated with blunted cortisol and cardiovascular responses to stress across both men and women. Men exhibited larger cortisol responses to stress than women. Co-users had significantly larger stress-related increases in cannabis craving than cannabis-only users. Cannabis users reported smaller increases in anxiety during stress than cannabis non/light-users, and both male nicotine-only users and male cannabis-only users experienced significantly smaller increases in stress than their non/light-user control counterparts. This study replicates and extends earlier research on the impacts of sex and nicotine use on stress responses, and it provides novel findings suggesting that when co-used with nicotine, cannabis use may not confer additional alterations to physiological nor subjective responses to stress. Co-use, however, was associated with enhanced stress-related craving for cannabis.

Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency.

The Effects of Nicotine and Cannabis Co-Use During Late Adolescence on White Matter Fiber Tract Microstructure

Co-use of cannabis and nicotine and tobacco products (NTPs) in adolescence/young adulthood is common and associated with worse outcomes than the use of either substance in isolation. Despite this, little is known about the unique contributions of co-use to neurostructural microstructure during this neurodevelopmentally important period. This study sought to investigate the interactive effects of nicotine and cannabis co-use on white matter fiber tract microstructure in emerging adulthood. A total of 111 late adolescent (16-22 years old) nicotine (NTP; n = 55, all past-year cannabis users) and non-nicotine users (non-NTP; n = 56, 61% reporting cannabis use in the past year) completed demographic and clinical interviews and a neuroimaging session comprising anatomical and diffusion-weighted imaging scans. Group connectometry analysis identified white matter tracts significantly associated with the interaction between nicotine group and past-year cannabis use according to generalized fractional anisotropy (GFA). Nicotine Group × Cannabis Use interactions were observed in the right and left cingulum and left fornix tracts (false discovery rate = 0.053), where greater cannabis use was associated with increased GFA in the cingulum and left fornix, but only when co-used with nicotine. This report represents the first group connectometry analysis in late adolescent/young adult cannabis and/or NTP users. Results suggest that co-use of cannabis and NTPs results in a structurally distinct white matter phenotype as compared with cannabis use only, although to what extent this may change over time with more chronic nicotine and cannabis use remains to be examined in future work.

Chronic Cannabis Users: A New Special Population to Consider for Drug Development.

The use and acceptance of cannabis, either medically or recreationally, has substantially outpaced the collection of data necessary to evaluate it's use in any population. However, the mere widespread availability does not imply the absence of risk or confirmation of efficacy and should not be treated as such. There is enough data to suggest that not only does the potential for pharmacokinetic and metabolic interactions exist, but also that baseline characteristics for a given population could be different in chronic cannabis users. Either or both of these may impact the safety and efficacy profile for any new drug in development. As such, we encourage drug developers to consider that the cannabis user may very well be a special population that warrants its own clinical pharmacology evaluation.

Clinical Management of Sleep and Sleep Disorders With Cannabis and Cannabinoids: Implications to Practicing Psychiatrists.

Phytocannabinoid derivatives are among the several compounds found in the cannabis plant. The phytocannabinoid chemicals Δ9-tetrahydrocannabinol (THC) and cannabidiol are mostly responsible for the drug's behavioral effects. Chronic cannabis administration has been shown to disrupt circadian rhythms and reduce the duration of the deepest phase (stage N3) of nonrapid eye movement sleep. Cannabidiol is thought to be responsible for the disruption of the circadian rhythm, whereas THC is thought to be accountable for the changes in sleep architecture. The quality of one's sleep has a significant impact on cannabis abstinence or relapse. As a result, the diminished sleep-promoting efficiency of cannabis in chronic users, as well as the resulting sleep difficulties once cannabis use is stopped, may sabotage attempts to quit and raise the risk of relapse. In individuals with obstructive sleep apnea who do not complain about the treatment process known as continuous positive airway pressure, cannabinoids are one of the treatments being considered. In this regard, preclinical investigations have demonstrated that combining the agent oleamide and THC aids in the stabilization of respiration in all stages of sleep as well as the maintenance of autonomic stability during sleep. The synthetic THC dronabinol was found to lower the apnea-hypopnea index in a clinical investigation and is regarded safe for the short-term treatment of obstructive sleep apnea. Patients experiencing nightmares who had been diagnosed with posttraumatic stress disorder were given the synthetic endocannabinoid receptor agonist nabilone. When compared with a placebo, the chemical proved helpful in reducing the frequency of nightmares. It is worth noting that a single study that looked at the effects of cannabidiol on REM behavior disorder found that symptoms improved. Based on the available findings, cannabinoids can be used as an alternate treatment for various sleep disorders. However, additional research is needed to corroborate the conclusions of these investigations.

Functional brain connectomes reflect acute and chronic cannabis use

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.

Effort-based decision making and self-reported apathy in frequent cannabis users and healthy controls: A replication and extension

ABSTRACT Introduction Amotivational syndrome is a term used to refer to lack of motivation and passive personality related to chronic cannabis use. Given mixed findings, the current study aimed to replicate and extend previous research on frequent cannabis use, motivated behavior, and self-reported apathy. Method Cannabis users (on average, ≥3 days/week of cannabis use over the past year), and healthy controls (≤1 day/month of cannabis use over the past year) completed the Apathy Evaluation Scale (AES), and the Effort Expenditure for Rewards Task (EEfRT). Repeated measures analysis of covariance was used to 1) examine the effects of group, reward magnitude, probability, and their interaction on hard task selections on the EEfRT, and 2) examine between-group differences on the AES, controlling for alcohol use and depressive symptoms. Results There were significant main effects of reward magnitude, probability, and an interaction between reward magnitude and probability on hard task selection (p’s < 0.05). Specifically, as reward magnitude and probability of winning the reward increased, participants were more likely to select hard tasks on the EEfRT. Relative to healthy controls, cannabis users were significantly more likely to select hard tasks on the EEfRT (F(1,56) = 6.49, p = 0.014, ηp 2 = 0.10). When controlling for alcohol use and depressive symptoms, no significant group differences in self-reported apathy were present (p = 0.46). Conclusions Cannabis users exhibit a greater likelihood of exerting more effort for reward, suggesting enhanced motivation relative to healthy controls. Thus, the current results do not support amotivational syndrome in adult frequent cannabis users. Despite some harms of long-term cannabis use, amotivation may not be among them.

Abstract TP174: Cannabis And Stroke Outcomes: A National Registry Analysis

Introduction: Recreational and medical cannabis use in the United States has been increasing in recent years in light of state efforts to decriminalize and legalize its use. Its legal status has long precluded extensive research into its adverse effects, especially as it pertains to the realm of vascular and cerebrovascular outcomes. To date, minimal research has been completed on the sequelae of cannabis in cerebrovascular hospital admissions. Methods: A query of the 2012-2015 Nationwide Inpatient Sample searched for patients admitted with cerebrovascular related ICD-9 diagnoses. These patients were then grouped by the presence of concurrent diagnosis of cannabis use disorder, and compared with respect to various peri- and postoperative complications, all-cause mortality, discharge disposition, length of stay, and hospitalization costs. Propensity score matching was utilized to control for potential baseline confounders. Results: A total of 900,023 patients met inclusion/exclusion criteria, 7,231 (0.80%) of whom had cannabis use disorder. After controlling for baseline characteristics, these patients had higher rates of inpatient mortality (odds ratio [OR] 1.99; p=0.034), and non-routine discharge, as well as increased lengths of stay (6.3 vs 5.9 days, p&lt;0.001) and no significant difference in hospitalization charges ($63805 vs. $ 63328 10, p=0.6777). Conclusions: Based on a national trends analysis, chronic cannabis use appears to be associated with increased perioperative morbidity and mortality among patients admitted for cerebrovascular diagnoses. Physicians should ensure that a thorough drug use history is taken, and that affected patients be adequately informed of associated risks. Further research can elucidate further the effect on specific cerebrovascular diagnoses such as stroke and aneurysms.

Attenuated Psychotic Symptoms in Adolescents With Chronic Cannabis and MDMA Use.

ObjectivesBoth substance use, on the one hand, and the first signs of psychosis, on the other, commonly begin in adolescence. Adolescents with substance use disorder (SUD) frequently show recreational use of cannabis and 3,4-methylenedioxymethamphetamine (MDMA). When attenuated psychotic symptoms (APS) occur during the course of SUD, they are commonly attributed to the cannabis use, neglecting the role of other substances abused, such as MDMA in the risk of psychosis.MethodsWe analyzed retrospective self-reports on APS (Prodromal Questionnaire, PQ-16) and amount of cannabis and MDMA use in n = 46 adolescent psychiatry outpatients with SUD. N = 17 (35%) individuals reported MDMA consume additional to cannabis. Furthermore, we examined the associations of APS with cannabis and MDMA use in stepwise hierarchical regressions while controlling for trauma history, birth complications and gender.ResultsAPS were not related to cannabis (B = 0.04, p = 0.842), but to MDMA use (B = 4.88, p = 0.001) and trauma history (B = 0.72, p = 0.001). Gender (B = −0.22, p = 0.767) and birth complications (B = −0.68, p = 0.178) were not associated with APS.DiscussionOur results indicate that MDMA use additional to cannabis use is associated with APS among adolescent SUD patients. Contrary to our expectations, we did not see an association of cannabis use and APS. We speculate that cannabis increases the risk for psychosis after a longer period of use and in combination with other risk factors, such as trauma history. Clinicians should screen for APS among SUD patients using MDMA and cannabis in order to adapt treatment plans of SUDs. Future research should validate these findings in longitudinal studies including polysubstance use and trauma history.

Chronic pain and medical cannabis: Narrative review and practice considerations in persons living with HIV

AbstractGlobally, 38 million persons live with human immunodeficiency virus (HIV) (PLWH), and a significant portion live with chronic pain. While not yet fully characterized, preliminary data suggest 40%‐83% of PLWH experience chronic pain, and many report undertreatment. A growing body of literature suggests undertreatment of chronic pain in PLWH leads to adverse clinical outcomes, such as poor retention in HIV care, suboptimal adherence to antiretroviral therapy, and increased use of intravenous drug use (eg, heroin). Chronic pain experienced by PLWH ranges from neuropathic to musculoskeletal with different etiologies and treatment modalities for each. Although opioids have been used to achieve analgesia in PLWH, there is growing interest in alternative pain therapies. Recently, medical cannabis (delta‐9‐tetrahydrocannabinol [THC] and cannabidiol [CBD]) products have been of high interest. Anecdotal evidence exists for medical cannabis and pain relief; however, robust clinical trial data are limited due to scheduling restrictions within the United States. The purposes of this narrative review are to summarize key literature for pain in PLWH and medical cannabis, discuss pertinent dosage forms and dosing schedules, and summarize safety and efficacy considerations for PLWH. Finally, the authors provide recommendations on cannabis rescheduling and pharmacists' and healthcare providers' roles in its prescribing and indication. Medical cannabis and pharmaceutical preparations containing both THC and CBD are a viable alternatives to opioid analgesics in the treatment of neuropathic pain in PLWH. The risks of misuse and cannabis use disorder warrant careful consideration, yet the benefits of effective analgesia associated with cannabis may outweigh these risks. Cannabis rescheduling and subsequent expansions in pain management research are warranted, particularly for CBD‐predominant and CBD‐isolate medical cannabis products.

Cerebral atrophy and cognitive impairment in a young patient with chronic cannabis use − a case report

Cannabis is known to mankind for ages. It was used as a medicine, an aphrodisiac, and a euphoriant. The psychotropic and neuromodulatory effects associated with cannabis use are extensively studied topics in the recent past. The authors report a case of cognitive impairment and cerebral atrophy in a young male patient with chronic cannabis use.

The Relationship Between Cannabis, Cognition, and Schizophrenia: It's Complicated.

The consequences of cannabis use, especially in the context of schizophrenia, have gained increased importance with the legalization of cannabis in North America and across the globe. Cannabis use has multifaceted impacts on cognition in schizophrenia patients and healthy subjects. Healthy subjects, particularly those who initiated cannabis use at earlier ages and used high-potency cannabis for longer durations, exhibited poorer cognition mainly in working memory and attention. Cannabis use in schizophrenia has been associated with symptom exacerbation, longer and more frequent psychotic episodes, and poorer treatment outcomes. However, cannabis-using patients have better overall cognitive performance compared to patients who were not cannabis users. Interestingly, these effects were only apparent in lifetime cannabis users, but not in current (or within last 6months) users. Moreover, higher frequency and earlier age of cannabis use initiation (i.e., before 17years of age) were associated with better cognitive performance, although they had an earlier illness onset. Three possible hypotheses seem to come forward to explain this paradox. First, some components of cannabis may have antipsychotic or cognitive-enhancing properties. Secondly, chronic cannabis use may alter endocannabinoid signaling in the brain which could be a protective factor for developing psychosis or cognitive impairments. A third explanation could be their representation of a phenotypically distinct patient group with more intact cognitive functioning and less neurodevelopmental pathology. Multiple factors need to be considered to understand the complex relationship between cannabis, cognitive function, and schizophrenia. In short, age at initiation, duration and rate of cannabis use, abstinence duration, co-use of substances and alcohol, prescribed medications, relative cannabinoid composition and potency of cannabis, presence of genetic and environmental vulnerability factors are prominent contributorsto the variability in outcomes. Animal studies support the disruptive effects of Δ9-tetrahydrocannabinol (THC) administration during adolescence on attention and memory performance. They provide insights about interaction of cannabinoid receptors with other neurotransmitter systems, such as GABA and glutamate, and other regulatory molecules, such as PSD95 and synaptophysin. Cannabidiol (CBD), on the other hand, can improve cognitive deficits seen in neurodevelopmental and chemically-induced animal models of schizophrenia. Future studies focusing on bridging the translational gaps between human and animal studies, through the use of translationally relevant methods of exposure (e.g., vaping), consistent behavioral assessments, and congruent circuit interrogations (e.g., imaging) will help to further clarify this complex picture.