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Cannabis use and other illicit drug use: testing the cannabis gateway hypothesis.

AIM: To examine the associations between the frequency of cannabis use and the use of other illicit drugs. DESIGN: A 25-year longitudinal study of the health, development and adjustment of a birth cohort of 1,265 New Zealand children. MEASUREMENTS: Annual assessments of the frequency of cannabis use were obtained for the period 14-25 years, together with measures of the use of other illicit drugs from the same time period. FINDINGS: The frequency of cannabis use was associated significantly with the use of other illicit drugs, other illicit drug abuse/dependence and the use of a diversity of other drugs. This association was found to be particularly strong during adolescence but declined rapidly as age increased. Statistical control for confounding by both fixed and time dynamic factors using random- and fixed-effects regression models reduced the strength of association between frequency of cannabis use and other illicit drug use, but a strong association between frequency of cannabis use and other illicit drug use remained even after control for non-observed and time-dynamic sources of confounding. CONCLUSIONS: Regular or heavy cannabis use was associated with an increased risk of using other illicit drugs, abusing or becoming dependent upon other illicit drugs, and using a wider variety of other illicit drugs. The risks of use, abuse/dependence, and use of a diversity of other drugs declined with increasing age. The findings may support a general causal model such as the cannabis gateway hypothesis, but the actual causal mechanisms underlying such a gateway, and the extent to which these causal mechanisms are direct or indirect, remain unclear.

Adolescent↗

Non-smoked cannabis consumption formats and Cannabis Use Disorder severity in an illicit setting: Evidence from Chile, 2020-2024.

BACKGROUND: Cannabis Use Disorder (CUD) has become an increasing public health burden, particularly in Chile. Non-smoked cannabis formats and products have been independently associated with CUD but remain understudied in the region. This study compares CUD severity among individuals aged 12 to 65 in Chile who consume cannabis via edibles, vaporization or both versus those who exclusively smoke it. METHODS: We obtained secondary data from three waves of the Chilean National Survey on Drugs in the General Population (ENPG), a three-stage stratified probabilistic sampling design study conducted in 2020, 2022, and 2024. Our pooled cross-sectional sample included individuals (n = 3543) who reported cannabis use in vaped, edible, both vaped and edible or exclusively smoked format in the past 12 months. We used a partial proportional odds model to estimate the association between CUD severity and consumption formats. RESULTS: Cannabis vaping group showed higher odds of presenting at least mild CUD (OR = 6.21 [95% CI: 3.75-10.3]), as did the edible group (OR = 1.73 [95% CI: 1.08-2.78]) and both group (OR = 5.92 [95% CI: 2.72-12.87]), compared to exclusive smokers. However, only the vaped group demonstrated higher odds for all severity levels. CONCLUSION: Compared with exclusive smokers, users of vaporizers and/or edibles showed a stronger association with CUD. This association may be explained by consumption patterns and total THC exposure. Further research is needed to characterize the average THC exposure by consumption format, acknowledging contextual confounders such as the legal framework.

Humans↗

Induction of sister-chromatid exchanges in heroin-cannabis, heroin and cannabis addicts.

The aim of this study was to determine the frequency of sister-chromatid exchanges (SCEs) in heroin-cannabis, heroin and cannabis addicts. The group of 84 subjects consisted of 42 controls, 16 heroin-cannabis addicts, 12 heroin addicts and 14 cannabis addicts. The mean number of SCEs/cell was 12.95 in heroin-cannabis addicts, 12.05 in heroin addicts and 11.99 in cannabis addicts. These values are significantly (P less than 0.002) higher than the mean values found in controls. This increase in SCEs may be related to reduced DNA repair in chronic drug addicts, which would allow the fixation or retention of a greater fraction of the DNA lesions caused by normal environmental exposure.

Adult↗

Neurophysiology of motor function following cannabis discontinuation in chronic cannabis smokers: an fMRI study.

The objective of this study was to identify the differences in cerebral activation between chronic cannabis smokers and controls in response to finger sequencing. We hypothesized that attentional areas related to motor function as well as primary and supplementary motor cortices would show diminished activation in chronic cannabis smokers. Nine cannabis smokers and 16 controls were included in these analyses. Scanning was performed on a GE 1.5T scanner. Echo planar images and high-resolution MR images were acquired. The challenge paradigm included left and right finger sequencing. Group differences in cerebral activation were examined for Brodmann areas (BA) 4, 6, 24, and 32 using ROI analyses in SPM. Cannabis users, tested within 4-36 h of discontinuation, exhibited significantly less activation than controls in BA 24 and 32 bilaterally during right- and left-sided sequencing and for BA 6 in all tasks except for left-sided sequencing in the left hemisphere. There were no statistically significant differences for BA 4. None of these regional activations correlated with urinary cannabis concentration and verbal IQ for smokers. These results suggest that recently abstinent chronic cannabis smokers produce reduced activation in motor cortical areas in response to finger sequencing compared to controls.

Adult↗

Cannabis prices and dynamics of cannabis use.

This paper uses duration models and self-reported cannabis histories from young Australians to study the dynamics of cannabis use. We find that low cannabis prices are associated with early initiation into cannabis use. While the decision to quit does not appear to be directly influenced by price, we find that the younger an individual is when they start using cannabis the less likely they are to quit. Therefore, low cannabis prices lead to early use and because of that they lead to a low quit rate and hence a longer duration of use.

Adolescent↗

Cannabis withdrawal among non-treatment-seeking adult cannabis users.

This study investigates the clinical significance of a cannabis withdrawal syndrome in 104 adult, non-treatment-seeking, primarily cannabis users who reported at least one serious attempt to stop using cannabis. Retrospective self-report data were obtained on eighteen potential cannabis withdrawal symptoms derived from the literature, including co-occurrence, time course, and any actions taken to relieve the symptom. Study findings provide evidence for the clinical significance of a cannabis withdrawal syndrome, based on the high prevalence and co-occurrence of multiple symptoms that follow a consistent time course and that prompt action by the subjects to obtain relief, including serving as negative reinforcement for cannabis use.

Adult↗

Cannabis control. An approach to cannabis use and dependence.

BACKGROUND: Cannabis use is widespread in our community. Dependence on cannabis may be associated with significant mental and physical harms. OBJECTIVE: This article aims to give an overview of the adverse effects of cannabis use and guidelines for management of cannabis dependence. DISCUSSION: General practitioners can manage cannabis dependence from a harm minimisation framework using motivational interviewing and other counselling measures. Occasionally, pharmacologic approaches may be used with the caveat that they should be brief and carefully monitored.

Adult↗

Divided attention performance in cannabis users and non-users following alcohol and cannabis separately and in combination.

The effect of delta 9-tetrahydrocannabinol (delta 9-THC) and alcohol, singly and in combination, on divided attention performance was investigated in cannabis users and non-users who were matched for alcohol use. Both cannabis and alcohol produced decrements in central and peripheral signal detections. Drug and alcohol effects were greater for signal presentations in the periphery. Cannabis users were less impaired in peripheral signal detection than non-users while intoxicated by cannabis and/or alcohol. These findings suggest the development of tolerance and cross-tolerance in regular cannabis users and/or the ability to compensate for intoxication effects.

Adult↗

A comparison of the latent class structure of cannabis problems among adult men and women who have used cannabis repeatedly.

BACKGROUND: Little empirical evidence exists to determine if there are alternative classification schemes for cannabis abuse and dependence beyond the definitions provided by Diagnostic and Statistical Manual (DSM) criteria. Current evidence is not conclusive regarding gender differences for cannabis use, abuse and dependence. It is not known if symptom profiles differ by gender. METHODS: Latent class analysis (LCA) was used to assess whether cannabis abuse and dependence symptom patterns suggest a severity spectrum or distinct subtypes and to test whether symptom patterns differ by gender. Data from 3312 men and 2509 women in the National Longitudinal Alcohol Epidemiologic Survey (NLAES) who had used cannabis 12 + times life-time were included in the present analyses. The comparability of the solutions for men and women was examined through likelihood ratio chi(2) tests. RESULTS: Based on the Bayesian information criterion and interpretability, a four-class solution was selected, and the classes were labeled as 'unaffected/mild hazardous use', 'hazardous use/abuse', 'abuse/moderate dependence' and 'severe abuse/dependence'. The solutions were generally suggestive of a severity spectrum. Compared to men, women were more likely to be in the 'unaffected/mild hazardous use' class and less likely to be in the 'abuse/moderate dependence' or 'severe abuse/dependence' classes. The results were generally similar for men and women. However, men had consistently and substantially higher endorsements of hazardous use than women, women in the 'abuse/moderate dependence' class had moderately higher rates for four dependence symptoms, and women in two of the classes were more likely to endorse withdrawal. CONCLUSION: Our findings generally support the severity dimension for DSM-IV cannabis abuse and dependence symptomatology for both men and women. While our results indicate that public health messages may have generic and not gender-specific content, treatment providers should focus more effort on reducing hazardous use in men and alleviating withdrawal in women.

Adolescent↗

Are cannabis users exposed to other drug use opportunities? Investigation of high-risk drug exposure opportunities among young cannabis users in London.

In a study of young cannabis users attending further education colleges across London which specifically excluded young heroin users or injecting drug users, 35% were found to have been offered heroin, 36% had been present during heroin smoking, and 12% present at injecting. Factors associated with these exposure opportunities were investigated. The proportion of friends who use drugs other than cannabis was also considered, both as an indicator of risk in its own right and as a possible mechanism for high-risk drug exposure opportunities involving heroin and/or injecting. Alcohol variables and interactional problems perceived by the study subjects to be caused by their own drug use were found to be predictive of the involvement of friends in drug use other than cannabis and of exposure to heroin and injecting drug use. Non-cannabis illicit drug use among friends was also found to be associated with offers of heroin and with having been present during injecting drug use by others. Interpretations of these data are considered and the need for more detailed study with an area of increasing public policy significance is discussed.

Adolescent↗

Identification and differentiation of resinous cannabis and textile cannabis: combined use of HPLC and high-resolution GLC.

The combined use of high-pressure liquid chromatography (HPLC) and high-resolution gas-liquid chromatography (GLC) afforded a means of isolating three substances in samples of cannabis, of determining their retention times in HPLC and in GLC with and without derivation, and of identifying them, by comparison with the data in the literature, with the three major constituents of cannabis: cannabidiol (CBD), delta-9-tetrahydrocannabinol (delta-9-THC) and cannabinol (CBN), without using either control substances or a mass spectrometer. Furthermore, calculation of the peak area ratios (formula: see text); for the different sample varieties can serve as a criterion for the differentiation of resinous cannabis and textile cannabis.

Cannabidiol↗

Preventing cannabis users from driving under the influence of cannabis.

Face-to-face, structured interviews were conducted with 320 recent cannabis users in New South Wales, Australia to assess the likely deterrent effects of (a) increasing the certainty of apprehension for driving under the influence of cannabis (DUIC) and (b) doubling the severity of penalties for DUIC. Participants were presented with a drug-driving scenario and asked to indicate their likelihood of driving given that scenario. The perceived risk of apprehension and severity of punishment were manipulated in each scenario to create four different certainty/severity conditions and participants were randomly allocated to one of these four groups. A subsidiary aim was to assess the likely impact of providing factual information about the accident risk associated with DUIC. Recent drug drivers who felt at low risk of accident when DUIC were asked to rate their willingness to drive if convinced that it was dangerous. The results suggested that increasing the certainty but not severity of punishment would produce reductions in cannabis-intoxicated driving among recent cannabis users. Providing factual information about the risks associated with DUIC would appear to have little impact on drug-driving rates among this population.

Accidents, Traffic↗

Two cases of "cannabis acute psychosis" following the administration of oral cannabis.

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Acute Disease↗

Divided attention performance of cannabis users and non-users following cannabis and alcohol.

The effects of delta9-tetrahydrocannabinol (delta9-THC) and alcohol, and their combination, on divided attention performance were compared for cannabis users and non-users of both sexes. Performance by all subjects was significantly impaired following 2.6 and 5.2 mg delta9-THC but not at blood alcohol concentrations of 48 and 96 mg/100 ml. The combined effect of the 2 drugs depended upon prior experience with cannabis. A synergistic action occurred in non-users while an antagonistic effect occurred in the group of users. Differences in the alcohol effects between users and non-users provided evidence of cross-tolerance between cannabis and alcohol.

Adult↗

Cannabis intoxication: effects of monetary incentive on performance, a controlled investigation of behavioural tolerance in moderate users of cannabis.

The study examined the effect of monetary incentive on the performance of five tasks after two heterogeneous groups of experienced users of cannabis and previously naive subjects had smoked placebo material and two dose levels of cannabis. The performance of the motivated subjects was compared with that of two non-motivated matched groups. Dose-related impairment was found on four of the five tasks, supporting previous findings of cannabis-induced impairment of short-term memory, goal-directed behavior and choice reaction times. Results for three of the tasks suggested that the performance of the motivated subjects was less affected by the drug than was the performance of the non-motivated subjects. There was no difference between the performance of subjects naive and experienced with respect to drug use.

Adult↗

Identification of Cannabis pollens using an allergic patient's immunoglobulin E and purification and characterization of allergens in Cannabis pollens.

Cannabis pollen allergens were detected using the serum of an allergic patient. The allergens were then purified by sequential column chromatography (including DE52 cellulose and phenyl-Sepharose CL-4B) and preparative HPLC. The molecular weight of the allergens were determined as 10,050 and 13,706 by matrix-assisted laser desorption/ionization time of flight mass spectrometry. We utilised Western blotting and development of an enzyme-linked immunosorbent assay for the detection of Cannabis pollen allergens.

Allergens↗

Chemotaxonomic features associated with flavonoids of cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) in relation to hops (Humulus lupulus L.).

The major flavonoids present in the leaves and flowers of the cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) cultivars Felina and Futura are orientin (1), vitexin (2), luteolin-7-O-beta-D-glucuronide (3), and apigenin-7-O-beta-D-glucuronide (4), while prenylated flavonoids, to which the potent estrogenicity of hops (Humilus lupulus L.) is associated, are absent. The different composition of flavonoids has chemotaxonomic value.

Apigenin↗

Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.

PURPOSE: To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS). PATIENTS AND METHODS: Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks. RESULTS: Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms. CONCLUSION: CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.

Administration, Oral↗