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Nature Reviews. Disease Primers Feb 2021Cannabis use disorder (CUD) is an underappreciated risk of using cannabis that affects ~10% of the 193 million cannabis users worldwide. The individual and public health... (Review)
Review
Cannabis use disorder (CUD) is an underappreciated risk of using cannabis that affects ~10% of the 193 million cannabis users worldwide. The individual and public health burdens are less than those of other forms of drug use, but CUD accounts for a substantial proportion of persons seeking treatment for drug use disorders owing to the high global prevalence of cannabis use. Cognitive behavioural therapy, motivational enhancement therapy and contingency management can substantially reduce cannabis use and cannabis-related problems, but enduring abstinence is not a common outcome. No pharmacotherapies have been approved for cannabis use or CUD, although a number of drug classes (such as cannabinoid agonists) have shown promise and require more rigorous evaluation. Treatment of cannabis use and CUD is often complicated by comorbid mental health and other substance use disorders. The legalization of non-medical cannabis use in some high-income countries may increase the prevalence of CUD by making more potent cannabis products more readily available at a lower price. States that legalize medical and non-medical cannabis use should inform users about the risks of CUD and provide information on how to obtain assistance if they develop cannabis-related mental and/or physical health problems.
Topics: Analgesics; Cannabis; Cognitive Behavioral Therapy; Humans; Marijuana Abuse; Prevalence
PubMed: 33627670
DOI: 10.1038/s41572-021-00247-4 -
Psychopharmacology Bulletin Jan 2021This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the... (Review)
Review
PURPOSE OF REVIEW
This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction.
RECENT FINDINGS
Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic.
SUMMARY
Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use.
Topics: Adolescent; Adult; Cannabinoids; Cannabis; Cognition; Humans; Marijuana Abuse; Medical Marijuana
PubMed: 33897066
DOI: No ID Found -
Pharmacology 2020Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in Cannabis sativa is tetrahydrocannabinol (THC). However, in the past 40... (Review)
Review
Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in Cannabis sativa is tetrahydrocannabinol (THC). However, in the past 40 years the content of the psychoactive ingredient THC in most of the preparations is not constant but has increased due to other breeding and culturing conditions. THC acts as the endocannabinoids at CB1 and CB2 receptors but pharmacologically can be described as a partial (not a pure) agonist. Recent evidence shows that activation of the CB1 receptor by THC can diminish the production of neuronal growth factor in neurons and affect other signalling cascades involved in synapsis formation. Since these factors play an important role in the brain development and in the neuronal conversion processes during puberty, it seems reasonable that THC can affect the adolescent brain in another manner than the adult brain. Accordingly, in adolescent cannabis users structural changes were observed with loss of grey matter in certain brain areas. Moreover, recent studies show different effects of THC on adolescent and adult brains and on behaviour. These studies indicate that early THC abuse can result in neuropsychological deficits. This review gives an overview over the present knowledge in this field.
Topics: Adolescent; Adult; Behavior; Brain; Cannabis; Dronabinol; Endocannabinoids; Humans; Marijuana Abuse; Receptors, Cannabinoid
PubMed: 32629444
DOI: 10.1159/000509377 -
Psychopharmacology Bulletin May 2020This is a comprehensive review of the association between cannabis use and psychological disorders. It reviews the latest and seminal evidence that is available and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
This is a comprehensive review of the association between cannabis use and psychological disorders. It reviews the latest and seminal evidence that is available and attempts to conclude the strength of such association.
RECENT FINDINGS
Cannabis is a flowering plant with psychoactive properties, attributed to cannabinoids that naturally occur within the plant. These act through the CB1 and CB2 receptors to inhibit GABA and glutamate release, as well through other forms of neuromodulation through the modulation of the endocannabinoid system (eCBs); a system that is otherwise involved in different pathways, including reward, memory, learning, and pain. Recent societal changes have increased the use of both medical and recreational cannabis. Patients with mental illness are considered more vulnerable and are prone to reward-seeking behavior. Cannabis use disorder (CUD) has been shown to have an increased prevalence in individuals with mental illness, creating an explosive cocktail. Approximately 1 in 4 patients with schizophrenia are also diagnosed with CUD. Cannabis use is associated with 2-4 times the likelihood of developing psychosis in healthy individuals. It has also been associated with multiple poor prognostic factors in schizophrenia, as well as in patients with a history of psychosis who do not meet diagnostic criteria for schizophrenia. Cannabis has been linked with anxiety; THC has been shown to elicit anxiety; however, anxiety is also a trigger for cannabis use. However, a recent large meta-analysis did not find a convincing link between cannabis and anxiety. This was reiterated in a recent epidemiological study that did not find such a correlation; however, it did identify a link between cannabis use, substance disorder, alcohol use disorder, drug use disorder, and nicotine dependence. Similarly, contradicting data exists regarding the link of depression and cannabis use.
SUMMARY
Cannabis use is increasing with recent societal shifts; however, its interaction with mental health is less well understood. CUD is highly prevalent in individuals with mental health disorders, especially those with other substance abuse disorders. There is evidence to support that cannabis use may trigger and worsen psychosis and schizophrenia. The link with depression and anxiety is less clear and needs further investigation. Personality disorder is linked with substance use disorder and shares similar risk factors with CUD.
Topics: Anxiety Disorders; Cannabis; Comorbidity; Humans; Marijuana Abuse; Psychotic Disorders; Substance-Related Disorders
PubMed: 32508368
DOI: No ID Found -
Addiction (Abingdon, England) Jul 2022Cannabis withdrawal is a well-characterized phenomenon that occurs in approximately half of regular and dependent cannabis users after abrupt cessation or significant... (Review)
Review
BACKGROUND AND AIMS
Cannabis withdrawal is a well-characterized phenomenon that occurs in approximately half of regular and dependent cannabis users after abrupt cessation or significant reductions in cannabis products that contain Δ -tetrahydrocannabinol (THC). This review describes the diagnosis, prevalence, course and management of cannabis withdrawal and highlights opportunities for future clinical research.
METHODS
Narrative review of literature.
RESULTS
Symptom onset typically occurs 24-48 hours after cessation and most symptoms generally peak at days 2-6, with some symptoms lasting up to 3 weeks or more in heavy cannabis users. The most common features of cannabis withdrawal are anxiety, irritability, anger or aggression, disturbed sleep/dreaming, depressed mood and loss of appetite. Less common physical symptoms include chills, headaches, physical tension, sweating and stomach pain. Despite limited empirical evidence, supportive counselling and psychoeducation are the first-line approaches in the management of cannabis withdrawal. There are no medications currently approved specifically for medically assisted withdrawal (MAW). Medications have been used to manage short-term symptoms (e.g. anxiety, sleep, nausea). A number of promising pharmacological agents have been examined in controlled trials, but these have been underpowered and positive findings not reliably replicated. Some (e.g. cannabis agonists) are used 'off-label' in clinical practice. Inpatient admission for MAW may be clinically indicated for patients who have significant comorbid mental health disorders and polysubstance use to avoid severe complications.
CONCLUSIONS
The clinical significance of cannabis withdrawal is that its symptoms may precipitate relapse to cannabis use. Complicated withdrawal may occur in people with concurrent mental health and polysubstance use.
Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Hallucinogens; Humans; Marijuana Abuse; Substance Withdrawal Syndrome
PubMed: 34791767
DOI: 10.1111/add.15743 -
The International Journal on Drug Policy Nov 2021This study aimed to determine the efficacy and acceptability of pharmacotherapies for cannabis use disorder (CUD). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine the efficacy and acceptability of pharmacotherapies for cannabis use disorder (CUD).
METHODS
We conducted a systematic review and frequentist network meta-analysis, searching five electronic databases for randomized placebo-controlled trials of individuals diagnosed with CUD receiving pharmacotherapy with or without concomitant psychotherapy. Primary outcomes were the reduction in cannabis use and retention in treatment. Secondary outcomes were adverse events, discontinuation due to adverse events, total abstinence, withdrawal symptoms, cravings, and CUD severity. We applied a frequentist, random-effects Network Meta-Analysis model to pool effect sizes across trials using standardized mean differences (SMD, g) and rate ratios (RR) with their 95% confidence intervals.
RESULTS
We identified a total of 24 trials (n=1912, 74.9% male, mean age 30.2 years). Nabilone (d=-4.47 [-8.15; -0.79]), topiramate (d=-3.80 [-7.06; -0.54]), and fatty-acid amyl hydroxylase inhibitors (d=-2.30 [-4.75; 0.15]) reduced cannabis use relative to placebo. Dronabinol improved retention in treatment (RR=1.27 [1.02; 1.57]), while topiramate worsened treatment retention (RR=0.62 [0.42; 0.91]). Gabapentin reduced cannabis cravings (d=-2.42 [-3.53; -1.32], while vilazodone worsened craving severity (d=1.69 [0.71; 2.66]. Buspirone (RR=1.14 [1.00; 1.29]), venlafaxine (RR=1.78 [1.40; 2.26]), and topiramate (RR=9.10 [1.27; 65.11]) caused more adverse events, while topiramate caused more dropouts due to adverse events.
CONCLUSIONS
Based on this review, some medications appeared to show promise for treating individual aspects of CUD. However, there is a lack of robust evidence to support any particular pharmacological treatment. There is a need for additional studies to expand the evidence base for CUD pharmacotherapy. While medication strategies may become an integral component for CUD treatment one day, psychosocial interventions should remain the first line given the limitations in the available evidence.
Topics: Adult; Female; Humans; Male; Marijuana Abuse; Network Meta-Analysis
PubMed: 34062288
DOI: 10.1016/j.drugpo.2021.103295 -
Toxins Feb 2021For thousands of years, has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the... (Review)
Review
For thousands of years, has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. More countries are legalizing the commercial production and sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic toxic effects of cannabis use on various body systems.
Topics: Animals; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Medical Marijuana; Nervous System; Neurotoxicity Syndromes; Plants, Toxic; Receptors, Cannabinoid; Signal Transduction
PubMed: 33562446
DOI: 10.3390/toxins13020117 -
Journal of Clinical Anesthesia Nov 2019According to the 2015 National Survey on Drug Use and Health, marijuana continues to be the most common illicit recreational drug used in the US. Cannabis is associated... (Review)
Review
According to the 2015 National Survey on Drug Use and Health, marijuana continues to be the most common illicit recreational drug used in the US. Cannabis is associated with systemic reactions that potentially affect perioperative outcomes. We have reviewed the most important pharmacological aspects and pathophysiological effects that should be considered during the perioperative management of chronic cannabis/cannabinoids users. The synthetic analogues provide higher potency with increased risk for complications. High cannabinoid liposolubility favors rapid accumulation in fatty tissue which prolongs its elimination up to several days after exposure. The multi-systemic effects of cannabinoids and their pharmacological interactions with anesthetic agents may lead to serious consequences. Low doses of cannabinoids have been associated with increased sympathetic response (tachycardia, hypertension and increased contractility) with high levels of norepinephrine detected 30 min after use. High doses enhance parasympathetic tone leading to dose-dependent bradycardia and hypotension. Severe vascular complications associated with cannabis exposure may include malignant arrhythmias, coronary spasm, sudden death, cerebral hypoperfusion and stroke. Bronchial hyperreactivity and upper airway obstruction are commonly reported in cannabis users. Postoperative hypothermia, shivering and increased platelet aggregation have been also documented.
Topics: Anesthetics; Cannabinoids; Drug Interactions; Humans; Marijuana Abuse; Perioperative Care; Postoperative Complications
PubMed: 30852326
DOI: 10.1016/j.jclinane.2019.03.011 -
JAMA Psychiatry Aug 2023Cannabis use is increasing worldwide and is suspected to be associated with increased risk of psychiatric disorders; however, the association with affective disorders...
IMPORTANCE
Cannabis use is increasing worldwide and is suspected to be associated with increased risk of psychiatric disorders; however, the association with affective disorders has been insufficiently studied.
OBJECTIVE
To examine whether cannabis use disorder (CUD) is associated with an increased risk of psychotic and nonpsychotic unipolar depression and bipolar disorder and to compare associations of CUD with psychotic and nonpsychotic subtypes of these diagnoses.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based cohort study using Danish nationwide registers included all individuals born in Denmark before December 31, 2005, who were alive, aged at least 16 years, and living in Denmark between January 1, 1995, and December 31, 2021.
EXPOSURE
Register-based diagnosis of CUD.
MAIN OUTCOME AND MEASURES
The main outcome was register-based diagnosis of psychotic or nonpsychotic unipolar depression or bipolar disorder. Associations between CUD and subsequent affective disorders were estimated as hazard ratios (HRs) using Cox proportional hazards regression with time-varying information on CUD, adjusting for sex; alcohol use disorder; substance use disorder; having been born in Denmark; calendar year; parental educational level (highest attained); parental cannabis, alcohol, or substance use disorders; and parental affective disorders.
RESULTS
A total of 6 651 765 individuals (50.3% female) were followed up for 119 526 786 person-years. Cannabis use disorder was associated with an increased risk of unipolar depression (HR, 1.84; 95% CI, 1.78-1.90), psychotic unipolar depression (HR, 1.97; 95% CI, 1.73-2.25), and nonpsychotic unipolar depression (HR, 1.83; 95% CI, 1.77-1.89). Cannabis use was associated with an increased risk of bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.54; 95% CI, 2.31-2.80), psychotic bipolar disorder (HR, 4.05; 95% CI, 3.52-4.65), and nonpsychotic bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.60; 95% CI, 2.36-2.85). Cannabis use disorder was associated with higher risk for psychotic than nonpsychotic subtypes of bipolar disorder (relative HR, 1.48; 95% CI, 1.21-1.81) but not unipolar depression (relative HR, 1.08; 95% CI, 0.92-1.27).
CONCLUSIONS AND RELEVANCE
This population-based cohort study found that CUD was associated with an increased risk of psychotic and nonpsychotic bipolar disorder and unipolar depression. These findings may inform policies regarding the legal status and control of cannabis use.
Topics: Male; Female; Humans; Bipolar Disorder; Depression; Cohort Studies; Prospective Studies; Marijuana Abuse; Substance-Related Disorders; Depressive Disorder, Major
PubMed: 37223912
DOI: 10.1001/jamapsychiatry.2023.1256 -
Dialogues in Clinical Neuroscience Sep 2020The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive... (Review)
Review
The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive behavior. Cannabis-derived psychoactive compounds such as Δ-tetrahydrocannabinol and synthetic cannabinoids directly interact with the reward system and thereby have addictive properties. Cannabinoids induce their reinforcing properties by an increase in tonic dopamine levels through a cannabinoid type 1 (CB) receptor-dependent mechanism within the ventral tegmental area. Cues that are conditioned to cannabis smoking can induce drug-seeking responses (ie, craving) by eliciting phasic dopamine events. A dopamine-independent mechanism involved in drug-seeking responses involves an endocannabinoid/glutamate interaction within the corticostriatal part of the reward system. In conclusion, pharmacological blockade of endocannabinoid signaling should lead to a reduction in drug craving and subsequently should reduce relapse behavior in addicted individuals. Indeed, there is increasing preclinical evidence that targeting the endocannabinoid system reduces craving and relapse, and allosteric modulators at CB receptors and fatty acid amide hydrolase inhibitors are in clinical development for cannabis use disorder. Cannabidiol, which mainly acts on CB and CB receptors, is currently being tested in patients with alcohol use disorder and opioid use disorder. .
Topics: Animals; Behavior, Addictive; Cannabinoids; Drug-Seeking Behavior; Endocannabinoids; Humans; Marijuana Abuse; Receptors, Cannabinoid; Reward
PubMed: 33162767
DOI: 10.31887/DCNS.2020.22.3/rspanagel