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.

What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?

Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.

Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of the AKT1 rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327, p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, where AKT1 genotype modulated the effect of THC.

These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.

The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.

We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.

Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d −0.20 to −0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.

Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is a dearth of experimental studies of the effects of the constituents of cannabis, such as Δ9-tetrahydrocannabinol (THC). In a study of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by THC to the consequent anxiety and neuropsychological impairment.

Twenty-two healthy adult males aged 28±6 years (mean±s.d.) participated in experimental sessions in which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the Baddeley Reasoning Task] within 45 min of injection.

THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive psychotic symptoms and deficits in working memory/executive function.

These findings confirm that THC can induce a transient, acute psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or cognitive impairment.