In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its ...constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.
Opioid use disorder (OUD) is reaching epidemic proportions worldwide, and is notoriously difficult to treat. Compassion focused therapy (CFT) has emerged as therapeutic tool for treating individuals ...exhibiting high levels of self-criticism and low self-esteem, both of which are common in OUD. Until now, however, there had been no research investigating this therapy in patients with OUD. Before running a premature clinical trial, it is important to fully assess the feasibility and acceptability of this treatment in this group of individuals. We aimed to assess the feasibility of CFT treatment in individuals with OUD in a short group intervention, which was co-created by the research team, service users and a local drugs service. The intervention involved three 2-hour sessions held over 3 weeks, where participants engaged in compassion-orientated psychoeducation and self-compassionate exercises. Individuals were randomly assigned to either the CFT group (n = 15), the active control (relaxation) group (n = 12) or the waitlist control group (n = 11). Of 103 individuals approached, 45% attended a baseline visit suggesting the treatment was acceptable to this group. A relatively low attrition rate across the 3 groups was found for CFT (21.1%), with no difference in drop-out between the groups. Qualitative analysis of interviews with participants identified a desire for more sessions. Compassion focused therapy was thus feasible and well-tolerated in those with OUD, and a further trial to evaluate any clinical differences may be warranted.
Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in ...increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control.
In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up.
Ninety-six participants (35 women; mean age, 44.07 years SD=10.59) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups.
This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.
ABSTRACT
Background ‘Recreational’ use of ketamine is spreading rapidly among young people. In healthy individuals an acute dose of the N‐methyl D‐aspartate (NMDA) receptor antagonist ketamine ...induces marked psychosis‐like effects and cognitive impairments, but little is known about the long‐term effects of the drug.
Aims To evaluate the long‐term neuropsychiatric or cognitive consequences.
Methods A total of 150 individuals were assessed, 30 in each of five groups: frequent ketamine users, infrequent ketamine users, abstinent users, polydrug controls and non‐users of illicit drugs. Twelve months later, 80% of these individuals were re‐tested.
Results Cognitive deficits were mainly observed only in frequent users. In this group, increasing ketamine use over the year was correlated with decreasing performance on spatial working memory and pattern recognition memory tasks. Assessments of psychological wellbeing showed greater dissociative symptoms in frequent users and a dose–response effect on delusional symptoms, with frequent users scoring higher than infrequent, abstinent users and non‐users, respectively. Both frequent and abstinent using groups showed increased depression scores over the 12 months.
Conclusions These findings imply that heavy use of ketamine is harmful to aspects of both cognitive function and psychological wellbeing. Health education campaigns need to raise awareness among young people and clinicians about these negative consequences of ketamine use.
Abstract The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. We conducted a pilot, randomised double blind placebo controlled study set out to assess the ...impact of the ad-hoc use of cannabidiol (CBD) in smokers who wished to stop smoking. 24 smokers were randomised to receive an inhaler of CBD (n = 12) or placebo (n = 12) for one week, they were instructed to use the inhaler when they felt the urge to smoke. Over the treatment week, placebo treated smokers showed no differences in number of cigarettes smoked. In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~ 40% during treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, combined with the strong preclinical rationale for use of this compound, suggest CBD to be a potential treatment for nicotine addiction that warrants further exploration.
Rationale
Whilst Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has been shown to enhance extinction learning in rats, its effects on fear memory in humans have not previously been studied.
...Objectives
We employed a Pavlovian fear-conditioning paradigm in order to assess the effects of CBD on extinction and consolidation.
Method
Forty-eight participants were conditioned to a coloured box (CS) with electric shocks (UCS) in one context and were extinguished in a second context. Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. At recall, 48 h later, participants were exposed to CSs and conditioning contexts before (recall) and after (reinstatement) exposure to the UCS. Skin conductance and shock expectancy measures of conditioned responding were recorded throughout.
Results
Successful conditioning, extinction and recall were found in all three treatment groups. CBD given post-extinction enhanced consolidation of extinction learning as assessed by shock expectancy. CBD administered at either time produced trend level reduction in reinstatement of autonomic contextual responding. No acute effects of CBD were found on extinction.
Conclusions
These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders.
Background
The two main constituents of cannabis, cannabidiol and δ
9
-tetrahydrocannabinol (THC), have opposing effects both pharmacologically and behaviourally when administered in the laboratory. ...Street cannabis is known to contain varying levels of each cannabinoid.
Aims
To study how the varying levels of cannabidiol and THC have an impact on the acute effects of the drug in naturalistic settings.
Method
Cannabis users (
n
= 134) were tested 7 days apart on measures of memory and psychotomimetic symptoms, once while they were drug free and once while acutely intoxicated by their own chosen smoked cannabis. Using an unprecedented methodology, a sample of cannabis (as well as saliva) was collected from each user and analysed for levels of cannabinoids. On the basis of highest and lowest cannabidiol content of cannabis, two groups of individuals were directly compared.
Results
Groups did not differ in the THC content of the cannabis they smoked. Unlike the marked impairment in prose recall of individuals who smoked cannabis low in cannabidiol, participants smoking cannabis high in cannabidiol showed no memory impairment. Cannabidiol content did not affect psychotomimetic symptoms, which were elevated in both groups when intoxicated.
Conclusions
The antagonistic effects of cannabidiol at the CB
1
receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC. In terms of harm reduction, users should be made aware of the higher risk of memory impairment associated with smoking low-cannabidiol strains of cannabis like ‘skunk’ and encouraged to use strains containing higher levels of cannabidiol.
Rationale
Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with ...reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use.
Objectives
The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users.
Methods
We measured dopamine synthesis capacity (indexed as the influx rate constant K
i
cer
) via 3,4-dihydroxy-6-
18
F-fluoro-
l
-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users.
Results
All subjects scored in excess of 34 points on the AES-S (median interquartile range 59.5 7.5), indicative of significant apathy based on normative data. K
i
cer
was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman’s rho = −0.64,
p
= 0.015 whole striatum; rho = −0.69,
p
= 0.006 associative) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho = 0.28,
p
= 0.34) or age of first cannabis use (rho = 0.25,
p
= 0.40).
Conclusions
These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.
ABSTRACT
Introduction Preliminary research has indicated that recreational ketamine use may be associated with marked cognitive impairments and elevated psychopathological symptoms, although no ...study to date has determined how these are affected by differing frequencies of use or whether they are reversible on cessation of use. In this study we aimed to determine how variations in ketamine use and abstention from prior use affect neurocognitive function and psychological wellbeing.
Method We assessed a total of 150 individuals: 30 frequent ketamine users, 30 infrequent ketamine users, 30 ex‐ketamine users, 30 polydrug users and 30 controls who did not use illicit drugs. Cognitive tasks included spatial working memory, pattern recognition memory, the Stockings of Cambridge (a variant of the Tower of London task), simple vigilance and verbal and category fluency. Standardized questionnaires were used to assess psychological wellbeing. Hair analysis was used to verify group membership.
Results Frequent ketamine users were impaired on spatial working memory, pattern recognition memory, Stockings of Cambridge and category fluency but exhibited preserved verbal fluency and prose recall. There were no differences in the performance of the infrequent ketamine users or ex‐users compared to the other groups. Frequent users showed increased delusional, dissociative and schizotypal symptoms which were also evident to a lesser extent in infrequent and ex‐users. Delusional symptoms correlated positively with the amount of ketamine used currently by the frequent users.
Conclusions Frequent ketamine use is associated with impairments in working memory, episodic memory and aspects of executive function as well as reduced psychological wellbeing. ‘Recreational’ ketamine use does not appear to be associated with distinct cognitive impairments although increased levels of delusional and dissociative symptoms were observed. As no performance decrements were observed in the ex‐ketamine users, it is possible that the cognitive impairments observed in the frequent ketamine group are reversible upon cessation of ketamine use, although delusional symptoms persist.
ABSTRACT
Aims Use of the stimulant drug mephedrone increased dramatically in 2009, and it is still available in the United Kingdom after being controlled in April 2010. This study aimed to assess ...mephedrone's acute cognitive and subjective effects.
Design A mixed within‐ and between‐subjects design compared 20 mephedrone users, first while intoxicated (T1) and secondly drug free (T2); and 20 controls twice when drug free (T1 and T2).
Settings Participants' own homes.
Participants Healthy adults recruited from the community.
Measurements Subjective effects, episodic and working memory, phonological and semantic fluency, psychomotor speed and executive control at were assessed at T1 and T2. Trait schizotypy, depression, changes in mephedrone use since the ban and attitudes influencing use of a hypothetical new legal high were indexed at T2 only.
Findings Compared with controls, mephedrone users had generally impaired prose recall (P = 0.037) and higher scores in schizotypy (P < 0.001) and depression (P = 0.01). Mephedrone acutely primed a marked ‘wanting’ for the drug (P < 0.001), induced stimulant‐like effects, impaired working memory (P < 0.001) and enhanced psychomotor speed (P = 0.024). Impulsivity in mephedrone users correlated with the number of hours in an average (nearly 8 hour) mephedrone session (r = 0.6). Users would be drawn to use a new legal high if it were pure, had no long/short term harms, and was positively rated by friends or on the internet.
Conclusions Mephedrone impairs working memory acutely, induces stimulant‐like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.
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