The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB1), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing.

We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning.

TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses.

TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.

Preclinical studies suggest that cannabidiol (CBD), a non-intoxicating phytocannabinoid, may reduce addiction-related behaviours for various drug classes in rodents, including ethanol, opiates, and psychostimulants. CBD modulates contextual memories and responses to reward stimuli. Nonetheless, research on the impact of CBD on cocaine addiction-like behaviors is limited and requires further clarification. This study tested the hypothesis that CBD administration inhibits the acquisition and retrieval of cocaine-induced conditioned place preference (CPP) in adult male and female C57BL6/J mice. We also ought to characterise a 5-day CPP protocol in these animals.

Male and female C57BL/6J mice were administered CBD (3, 10, and 30 mg/kg) 30 minutes before cocaine (15 mg/kg) acquisition of expression of CPP.

Cocaine induces a CPP in both female and male mice in the 5-day CPP protocol. CBD failed to prevent the acquisition or retrieval of place preference induced by cocaine. CBD did not decrease the time spent on the side paired with cocaine at any of the doses tested in male and female mice, in either acquisition or expression of contextual memory.

This study found no support for the hypothesis that CBD decreases reward memory involved in the formation of cocaine addiction. Further research is necessary to investigate the involvement of CBD in other behavioural responses to cocaine and other psychostimulant drugs. This study, however, characterised a 5-day CPP protocol for both female and male C57BL/6J mice.

This study seeks to determine the prevalence and nature of cannabis use in patients with headache in a tertiary headache clinic and to explore patients’ empiric experience in using cannabinoids therapeutically.

Many patients with headache report cannabinoid use as an effective abortive and/or preventive therapy. Mounting evidence implicates cannabinoids in pain mechanisms pertaining to migraine and other headache types.

A cross-sectional study surveyed 200 patients presenting with any headache disorder to a tertiary headache clinic in Calgary, Alberta. Descriptive analyses were applied to capture information about headache diagnoses and the frequency, doses and methods of cannabinoid delivery employed, as well as patients’ perceptions of therapeutic benefit and selected negative side effects.

Active cannabinoid users comprised 34.0% of respondents. Approximately 40% of respondents using cannabinoids engaged in very frequent use (≥300 days/year). Of cannabinoid modalities, liquid concentrates were most popular (39.2%), followed by smoked cannabis (33.3%). Patients endorsed cannabinoid use for both prevention and acute therapy of headaches, often concurrently. Sixty percent of respondents felt cannabinoids reduced headache severity, while 29.2% perceived efficacy in aborting headaches. Nearly 5% of respondents volunteered that they had encountered a serious problem such as an argument, fight, accident, or work issue as a result of their cannabis use. Approximately 35.4% of users had attempted to reduce their use.

This survey shows that over one-third of patients with headache disorders in a tertiary headache clinic use cannabis as a treatment for their headaches. Of these, about 25% and 60% perceive improvements in headache frequency and severity, respectively. The results of this survey will aid neurologists and headache specialists in understanding the landscape of cannabinoid use in a more severely affected population and inform future-controlled studies of cannabinoids in headache patients.

Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.

263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.

HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).

Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Cannabis use has increased dramatically across the country; however, few studies have assessed the long-term impact of medical cannabis (MC) use on cognition. Studies examining recreational cannabis users generally report cognitive decrements, particularly in those with adolescent onset. As MC patients differ from recreational consumers in motives for use, product selection, and age of onset, we assessed cognitive and clinical measures in well-characterized MC patients over 1 year. Based on previous findings, we hypothesized MC patients would not show decrements and might instead demonstrate improvements in executive function over time.

As part of an ongoing study, MC patients completed a baseline visit prior to initiating MC and evaluations following 3, 6, and 12 months of treatment. At each visit, patients completed a neurocognitive battery assessing executive function, verbal learning/memory, and clinical scales assessing mood, anxiety, and sleep. Exposure to delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) was also quantified.

Relative to baseline, MC patients demonstrated significant improvements on measures of executive function and clinical state over the course of 12 months; verbal learning/memory performance generally remained stable. Improved cognitive performance was not correlated with MC use; however, clinical improvement was associated with higher CBD use. Analyses suggest cognitive improvements were associated with clinical improvement.

Study results extend previous pilot findings, indicating that MC patients may exhibit enhanced rather than impaired executive function over time. Future studies should examine distinctions between recreational and MC use to identify potential mechanisms related to cognitive changes and the role of clinical improvement.

The aim of this study was to test the hypothesis that synthesis of nitric oxide (NO) and activation of CB1 receptors have opposite effects in a behavioural animal model of panic and anxiety.

To test the hypothesis, male Wistar rats were exposed to the elevated T-maze (ETM) model under the following treatments: L-Arginine (L-Arg) was administered before treatment with WIN55,212-2, a CB1 receptor agonist; AM251, a CB1 antagonist, was administered before treatment with L-Arg. All treatments were by intraperitoneal route.

The CB1 receptor agonist, WIN55,212-2 (1 mg/kg), induced an anxiolytic-like effect, which was prevented by pretreatment with an ineffective dose of L-Arg (1 mg/kg). Administration of AM251 (1 mg/kg), a CB1 antagonist before treatment with L-Arg (1 mg/kg) did not produce anxiogenic-like responses.

Altogether, this study suggests that the anxiolytic-like effect of cannabinoids may occur through modulation of NO signalling.

Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting.

We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24–36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression.

There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2–7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7–13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4–7.9; p < 0.0001).

In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

Medical cannabis has recently emerged as a treatment option for children with drug-resistant epilepsy. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about the attitudes of neurologists toward cannabinoid treatment of children with epilepsy.

A 21-item online survey was distributed via email to 148 pediatric neurologists working in hospitals and community clinics across Canada. Questions were related to clinical practice and demographics.

This survey achieved a response rate of 38% (56 Canadian neurologists). These neurologists were treating 668 pediatric epilepsy patients with cannabinoids. While 29% of neurologists did not support cannabis treatment in their patients, 34% prescribed cannabis, and 38% referred to another authorizing physician, mostly to community-based non-neurologists. The majority of neurologists considered cannabis for patients with Dravet syndrome (68%) and Lennox–Gastaut syndrome (64%) after an average of three failed anticonvulsants. Twenty-seven percent considered it for patients with idiopathic generalized epilepsy, and 18% for focal epilepsy. No neurologist used cannabis as a first-line treatment. All neurologists had at least one hesitation regarding cannabis treatment in pediatric epilepsy. The most common one was poor evidence (66%), followed by poor quality control (52%) and high cost (50%).

The majority of Canadian pediatric neurologists consider using cannabis as a treatment for epilepsy in children. With many gaps in evidence and high patient-driven demand for cannabis therapy, this survey provides immediate information from the “wisdom of the crowd,” to aid neurologists until further evidence is available.