Cannabis use and psychiatric and cogitive disorders: the chicken or the egg?

Forti, Marta Di; Morrison, Paul; Butt, Alexander; Murray, Robin M.

doi:10.1097/yco.0b013e3280fa838e

Cited by 106 publications

(64 citation statements)

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“…Also, elevated levels of the endocannabinoid anandamide have been detected in the cerebrospinal fluid of schizophrenics (Leweke et al, 1999(Leweke et al, , 2007Giuffrida et al, 2004). Moreover, frequent cannabis use significantly increases the risk for psychotic symptoms and schizophrenia (see for review, Di Forti et al, 2007;Leweke and Koethe, 2008). Supporting this hypothesis, glutamate transmission is tightly regulated by retrograde endocannabinoid signaling, and both the ECS and the glutamate are clearly involved in the pathophysiology of major symptoms of schizophrenia (Leweke and Koethe, 2008).…”

Section: Introductionmentioning

confidence: 89%

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats

et al. 2008

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Early maternal deprivation (MD) in rats (24 h, postnatal day 9-10) is a model for neurodevelopmental stress. There are some data proving that MD affects the endocannabinoid system (ECS) in a gender-dependent manner, and that these changes may account for the proposed schizophrenia-like phenotype of MD rats. The impact of MD on cannabinoid receptor distribution in the hippocampus is unknown. The aim of this study is to evaluate the expression of CB(1) and CB(2) receptors in diverse relevant subregions (DG, CA1, and CA3) of the hippocampus in 13-day-old rats by immunohistochemistry and densitometry. MD induced a significant decrease in CB(1) immunoreactivity (more marked in males than in females), which was mainly associated with fibers in the strata pyramidale and radiatum of CA1 and in the strata oriens, pyramidale, and radiatum of CA3. In contrast, MD males and females showed a significant increase in CB(2) immunoreactivity in the three hippocampal areas analyzed that was detected in neuropil and puncta in the stratum oriens of CA1 and CA3, and in the polymorphic cell layer of the dentate gyrus. A marked sex dimorphism was observed in CA3, with females exhibiting higher CB(1) immunoreactivity than males, and in dentate gyrus, with females exhibiting lower CB(2) immunoreactivity than males. These results point to a clear association between developmental stress and dysregulation of the ECS. The present MD procedure may provide an interesting experimental model to further address the role of the ECS in neurodevelopmental mental illnesses such as schizophrenia.

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Section: Introductionmentioning

confidence: 89%

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats

et al. 2008

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“…24 There is an increased risk of a psychosis in those who have ever used cannabis (pooled adjusted odds ratio = 1.41; 95% CI, 1.20-1.65) and a dose-response effect, with greater risk in subgroups consuming cannabis very frequently (pooled adjusted odds ratio = 2.09; 95% CI, 1.54-2.84). 54 These effects of cannabis may be consequent on its impact on the dopamine system.…”

Section: Discussionmentioning

confidence: 99%

“…If the criteria for severe major depressive disorder were met, the candidate was excluded from participation. Because the effects of cannabis can exacerbate mental illness 24,54 and have been linked to an increase in the risk of suicide, 22 candidates with a history or diagnosis of schizophrenia or bipolar depression were also excluded. Medical illnesses were also evaluated, and exclusion criteria included uncontrolled hypertension, cardiovascular disease, chronic pulmonary disease (eg, asthma, chronic obstructive pulmonary disease), and active substance abuse.…”

Section: Patientsmentioning

confidence: 99%

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Wilsey

Marcotte

Tsodikov

et al. 2008

The Journal of Pain

265

244

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The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. KeywordsNeuropathic pain; analgesia; cannabis; clinical trial; neuropsychological testingThe case for the clinical utility of cannabis as an analgesic derives from experimental studies as well as anecdotal reports. Activation of the endocannabinoid system suppresses HHS Public AccessAuthor manuscript J Pain. Author manuscript; available in PMC 2016 August 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript behavioral responses to acute and persistent noxious stimulation through both central 71 and peripheral 45 mechanisms. Cannabinoid receptors are localized in neuroanatomic regions intimately involved with transmission and modulation of pain signals: The periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), 40,66 and the dorsal horn of the spinal cord. 66 Animal experimentation has clearly demonstrated that synthetic and endogenous cannabinoids not only produce analgesia but also interact in some manner to potentiate opioids, 18,70 particularly in neuropathic pain. 41 Surveys involving the use of medicinal marijuana reveal that pain, sleep, and mood improve with only modest side effects. 72,73 In one human pain experiment, subjects had a significant dose-dependent antinociception (increased finger withdrawal latency) effect that was not reversed by opioid antagonism. 31 In a somewhat contradictory manner, hyperalgesic activity and enhancement of the perception of pain on acute exposure in chronic users of marijuana was reported. 20 Experience with cancer pain revealed that 120 mg codeine and 20 mg delta-9-tetrahydrocannabinol (9-THC) were similar to each other and significantly superior to placebo for the sum of the pain intensity differences and total pain relief. 55,56 However, there was a clear dose-response relationship for sedation, mental clouding, and other central nervous system (CNS) related side effects f...

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“…Because lifetime abstainers are by defi nition at no risk for SUDs and may differ systematically on other factors relevant to risks for psychopathology from lifetime drinkers (Liang et al, 2010;Skogen et al, 2011) or other drug users (Di Forti et al, 2007;Macleod et al, 2004), it was necessary to determine whether inclusion of abstainers in the comparison groups without the respective SUDs affected the sex-specifi c comorbid associations. Therefore, the logistic models for AUDs were refi t with lifetime abstainers (7.5% of men and 17.2% of women) excluded, and models for DUDs were refi t with those reporting no lifetime illicit drug use (68.8% of men, 77.8% of women) excluded.…”

Section: Assessmentsmentioning

confidence: 99%

Sex Differences in Prevalence and Comorbidity of Alcohol and Drug Use Disorders: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

Goldstein

Dawson

Chou

et al. 2012

J. Stud. Alcohol Drugs

102

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ABSTRACT. Objective:The present study examined sex differences in lifetime Axis I and II psychiatric comorbidity of DSM-IV alcohol use disorders (AUDs) and drug use disorders (DUDs) among general population U.S. adults. Method: Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, Wave 2 lifetime prevalences of each disorder comorbid with alcohol abuse, alcohol dependence, drug abuse, and drug dependence were compared between men and women. Sex-specifi c associations of alcohol, any drug, and cannabis-and cocaine-specifi c abuse and dependence with each comorbid disorder were examined using logistic regression, fi rst with adjustment for sociodemographic variables and then with additional adjustment for all other psychiatric disorders. Results: Prevalences of most comorbid disorders differed signifi cantly by sex among respondents with each AUD and DUD. However, after adjustment for sociodemographic characteristics and additional co-occurring psychiatric diagnoses, there were few sex differences in unique comorbid associations of specifi c AUDs and DUDs with specifi c psychiatric disorders. Conclusions: Rates of psychiatric disorders comorbid with AUDs and DUDs indicate large burdens of morbidity in both sexes, highlighting the need for careful assessment and appropriate treatment of both substance use and mental health disorders. The unique comorbid associations with AUDs and DUDs identifi ed in this study further indicate the need for prospective etiological research to characterize these associations, their underlying mechanisms, and the possible sex specifi city of those mechanisms. (J. Stud. Alcohol Drugs, 73, 938-950, 2012)

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Cannabis use and psychiatric and cogitive disorders: the chicken or the egg?

Cited by 106 publications

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Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Sex Differences in Prevalence and Comorbidity of Alcohol and Drug Use Disorders: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

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Cannabis use and psychiatric and cogitive disorders: the chicken or the egg?

Cited by 106 publications

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Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB1 and CB2 cannabinoid receptors of neonatal rats

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB1 and CB2 cannabinoid receptors of neonatal rats

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Sex Differences in Prevalence and Comorbidity of Alcohol and Drug Use Disorders: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

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Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB₁ and CB₂ cannabinoid receptors of neonatal rats