Smoking cannabis reduces obsessive-compulsive disorder (OCD) symptoms by half in the short-term

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People with obsessive-compulsive disorder, or OCD, report that the severity of their symptoms was reduced by about half within four hours of smoking cannabis, according to a Washington State University study.

The researchers analyzed data inputted into the Strainprint app by people who self-identified as having OCD, a condition characterized by intrusive, persistent thoughts and repetitive behaviors such as compulsively checking if a door is locked.

After smoking cannabis, users with OCD reported it reduced their compulsions by 60%, intrusions, or unwanted thoughts, by 49% and anxiety by 52%.

The study, recently published in the Journal of Affective Disorders, also found that higher doses and cannabis with higher concentrations of CBD, or cannabidiol, were associated with larger reductions in compulsions.

“The results overall indicate that cannabis may have some beneficial short-term but not really long-term effects on obsessive-compulsive disorder,” said Carrie Cuttler, the study’s corresponding author and WSU assistant professor of psychology.

“To me, the CBD findings are really promising because it is not intoxicating.

This is an area of research that would really benefit from clinical trials looking at changes in compulsions, intrusions and anxiety with pure CBD.”

The WSU study drew from data of more than 1,800 cannabis sessions that 87 individuals logged into the Strainprint app over 31 months. The long time period allowed the researchers to assess whether users developed tolerance to cannabis, but those effects were mixed.

As people continued to use cannabis, the associated reductions in intrusions became slightly smaller suggesting they were building tolerance, but the relationship between cannabis and reductions in compulsions and anxiety remained fairly constant.

Traditional treatments for obsessive-compulsive disorder include exposure and response prevention therapy where people’s irrational thoughts around their behaviors are directly challenged, and prescribing antidepressants called serotonin reuptake inhibitors to reduce symptoms.

While these treatments have positive effects for many patients, they do not cure the disorder nor do they work well for every person with OCD.

“We’re trying to build knowledge about the relationship of cannabis use and OCD because it’s an area that is really understudied,” said Dakota Mauzay, a doctoral student in Cuttler’s lab and first author on the paper.

Aside from their own research, the researchers found only one other human study on the topic: a small clinical trial with 12 participants that revealed that there were reductions in OCD symptoms after cannabis use, but these were not much larger than the reductions associated with the placebo.

The WSU researchers noted that one of the limitations of their study was the inability to use a placebo control and an “expectancy effect” may play a role in the results, meaning when people expect to feel better from something they generally do.

The data was also from a self-selected sample of cannabis users, and there was variability in the results which means that not everyone experienced the same reductions in symptoms after using cannabis.

However, Cuttler said this analysis of user-provided information via the Strainprint app was especially valuable because it provides a large data set and the participants were using market cannabis in their home environment, as opposed to federally grown cannabis in a lab which may affect their responses.

Strainprint’s app is intended to help users determine which types of cannabis work the best for them, but the company provided the WSU researchers free access to users’ anonymized data for research purposes.

Cuttler said this study points out that further research, particularly clinical trials on the cannabis constituent CBD, may reveal a therapeutic potential for people with OCD.

This is the fourth study Cuttler and her colleagues have conducted examining the effects of cannabis on various mental health conditions using the data provided by the app created by the Canadian company Strainprint.

Others include studies on how cannabis impacts PTSD symptoms, reduces headache pain, and affects emotional well-being.


Fear and anxiety are adaptive responses essential to coping with threats to survival. Yet excessive or persistent fear may be maladaptive, leading to disability. Symptoms arising from excessive fear and anxiety occur in a number of neuropsychiatric disorders, including generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and obsessive–compulsive disorder (OCD).

Notably, PTSD and OCD are no longer classified as anxiety disorders in the recent revision of the Diagnostic and Statistical Manual of Mental Disorders-5; however, excessive anxiety is central to the symptomatology of both disorders.

These anxiety-related disorders are associated with a diminished sense of well-being, elevated rates of unemployment and relationship breakdown, and elevated suicide risk [1–3].

Together, they have a lifetime prevalence in the USA of 29 % [4], the highest of any mental disorder, and constitute an immense social and economic burden [5, 6].

Currently available pharmacological treatments include serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressant drugs, and partial 5-hydroxytryptamine (5-HT)1A receptor agonists.

Anticonvulsants and atypical antipsychotics are also used to treat PTSD. These medications are associated with limited response rates and residual symptoms, particularly in PTSD, and adverse effects may also limit tolerability and adherence [7–10].

The substantial burden of anxiety-related disorders and the limitations of current treatments place a high priority on developing novel pharmaceutical treatments.

Cannabidiol (CBD) is a phytocannabinoid constituent of Cannabis sativa that lacks the psychoactive effects of ∆9-tetrahydrocannabinol (THC). CBD has broad therapeutic properties across a range of neuropsychiatric disorders, stemming from diverse central nervous system actions [11, 12].

In recent years, CBD has attracted increasing interest as a potential anxiolytic treatment [13–15]. The purpose of this review is to assess evidence from current preclinical, clinical, and epidemiological studies pertaining to the potential risks and benefits of CBD as a treatment for anxiety disorders.

CBD Pharmacology Relevant to Anxiety

General Pharmacology and Therapeutic Profile

Cannabis sativa, a species of the Cannabis genus of flowering plants, is one of the most frequently used illicit recreational substances in Western culture. The 2 major phyto- cannabinoid constituents with central nervous system activity are THC, responsible for the euphoric and mind-altering effects, and CBD, which lacks these psychoactive effects.

Preclinical and clinical studies show CBD possesses a wide range of therapeutic properties, including antipsychotic, analgesic, neuroprotective, anticonvulsant, antiemetic, antioxidant, anti-inflammatory, antiarthritic, and antineoplastic properties (see [11, 12, 16–19] for reviews).

A review of potential side effects in humans found that CBD was well tolerated across a wide dose range, up to 1500 mg/day (orally), with no reported psychomotor slowing, negative mood effects, or vital sign abnormalities noted [20].

CBD has a broad pharmacological profile, including interactions with several receptors known to regulate fear and anxiety-related behaviors, specifically the cannabinoid type 1 receptor (CB1R), the serotonin 5-HT1A receptor, and the transient receptor potential (TRP) vanilloid type 1 (TRPV1) receptor [11, 12, 19, 21].

In addition, CBD may also regulate, directly or indirectly, the peroxisome proliferator-activated receptor-γ, the orphan G-protein-coupled receptor 55, the equilibrative nucleoside transporter, the adenosine transporter, additional TRP channels, and glycine receptors [11, 12, 19, 21].

In the current review of primary studies, the following receptor-specific actions were found to have been investigated as potential mediators of CBD’s anxiolytic action: CB1R, TRPV1 receptors, and 5-HT1A receptors. Pharmacology relevant to these actions is detailed below.

The Endocannabinoid System

Following cloning of the endogenous receptor for THC, namely the CB1R, endogenous CB1R ligands, or “endocannabinoids” (eCBs) were discovered, namely anandamide (AEA) and 2-arachidonoylglycerol (reviewed in [22]). The CB1R is an inhibitory Gi/o protein-coupled receptor that is mainly localized to nerve terminals, and is expressed on both γ-aminobutryic acid-ergic and glutamatergic neurons.

eCBs are fatty acid derivatives that are synthesized on demand in response to neuronal depolarization and Ca2+ influx, via cleavage of membrane phospholipids. The primary mechanism by which eCBs regulate synaptic function is retrograde signaling, wherein eCBs produced by depolarization of the postsynaptic neuron activate presynaptic CB1Rs, leading to inhibition of neurotransmitter release [23].

The “eCB system” includes AEA and 2-arachidonoylglycerol; their respective degradative enzymes fatty acid amide hydroxylase (FAAH) and monoacylglycerol lipase; the CB1R and related CB2 receptor (the latter expressed mainly in the periphery); as well as several other receptors activated by eCBs, including the TRPV1 receptor, peroxisome proliferator-activated receptor-γ, and G protein-coupled 55 receptor, which functionally interact with CB1R signaling (reviewed in [21, 24]).

Interactions with the TRPV1 receptor, in particular, appear to be critical in regulating the extent to which eCB release leads to inhibition or facilitation of presynaptic neurotransmitter release [25]. The TRPV1 receptor is a postsynaptic cation channel that underlies sensation of noxious heat in the periphery, with capsacin (hot chili) as an exogenous ligand. TRPV1 receptors are also expressed in the brain, including the amygdala, periaqueductal grey, hippocampus, and other areas [26, 27].

The eCB system regulates diverse physiological functions, including caloric energy balance and immune function [28]. The eCB system is also integral to regulation of emotional behavior, being essential to forms of synaptic plasticity that determine learning and response to emotionally salient, particularly highly aversive events [29, 30].

Activation of CB1Rs produces anxiolytic effects in various models of unconditioned fear, relevant to multiple anxiety disorder symptom domains (reviewed in [30–33]). Regarding conditioned fear, the effect of CB1R activation is complex: CB1R activation may enhance or reduce fear expression, depending on brain locus and the eCB ligand [34]; however, CB1R activation potently enhances fear extinction [35], and can prevent fear reconsolidation.

Genetic manipulations that impede CB1R activation are anxiogenic [35], and individuals with eCB system gene polymorphisms that reduce eCB tone—for example, FAAH gene polymorphisms—exhibit physiological, psychological, and neuroimaging features consistent with impaired fear regulation [36].

Reduction of AEA–CB1R signaling in the amygdala mediates the anxiogenic effects of corticotropin-releasing hormone [37], and CB1R activation is essential to negative feedback of the neuroendocrine stress response, and protects against the adverse effects of chronic stress [38, 39].

Finally, chronic stress impairs eCB signaling in the hippocampus and amygdala, leading to anxiety [40, 41], and people with PTSD show elevated CB1R availability and reduced peripheral AEA, suggestive of reduced eCB tone [42].

Accordingly, CB1R activation has been suggested as a target for anxiolytic drug development [15, 43, 44]. Proposed agents for enhancing CB1R activation include THC, which is a potent and direct agonist; synthetic CB1R agonists; FAAH inhibitors and other agents that increase eCB availability, as well as nonpsychoactive cannabis phytocannabinoids, including CBD. While CBD has low affinity for the CB1R, it functions as an indirect agonist, potentially via augmentation of CB1R constitutional activity, or via increasing AEA through FAAH inhibition (reviewed in [21]).

Several complexities of the eCB system may impact upon the potential of CBD and other CB1R-activating agents to serve as anxiolytic drugs. First, CB1R agonists, including THC and AEA, have a biphasic effect: low doses are anxiolytic, but higher doses are ineffective or anxiogenic, in both preclinical models in and humans (reviewed in [33, 45]).

This biphasic profile may stem from the capacity of CB1R agonists to also activate TRPV1 receptors when administered at a high, but not low dose, as demonstrated for AEA [46]. Activation of TRPV1 receptors is predominantly anxiogenic, and thus a critical balance of eCB levels, determining CB1 versus TRPV1 activation, is proposed to govern emotional behavior [27, 47].

CBD acts as a TRPV1 agonist at high concentrations, potentially by interfering with AEA inactivation [48]. In addition to dose-dependent activation of TRPV1 channels, the anxiogenic versus anxiolytic balance of CB1R agonists also depends on dynamic factors, including environmental stressors [33, 49].

5-HT1A Receptors

The 5-HT1A receptor (5-HT1AR) is an established anxiolytic target. Buspirone and other 5-HT1AR agonists are approved for the treatment of GAD, with fair response rates [50]. In preclinical studies, 5-HT1AR agonists are anxiolytic in animal models of general anxiety [51], prevent the adverse effects of stress [52], and enhance fear extinction [53]. Both pre- and postsynaptic 5-HT1ARs are coupled to various members of the Gi/o protein family.

They are expressed on serotonergic neurons in the raphe, where they exert autoinhibitory function, and various other brain areas involved in fear and anxiety [54, 55]. Mechanisms underlying the anxiolytic effects of 5-HT1AR activation are complex, varying between both brain region, and pre- versus postsynaptic locus, and are not fully established [56].

While in vitro studies suggest CBD acts as a direct 5-HT1AR agonist [57], in vivo studies are more consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT1A signaling [58].

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/


More information: Dakota Mauzay et al, Acute Effects of Cannabis on Symptoms of Obsessive-Compulsive Disorder, Journal of Affective Disorders (2020). DOI: 10.1016/j.jad.2020.09.124

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