Changes in delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta‐analysis

Freeman, Tom P.; Craft, Sam; Wilson, Jack; Stylianou, Stephan; ElSohly, Mahmoud A.; Forti, Marta Di; Lynskey, Michael T.

doi:10.1111/add.15253

Cited by 159 publications

(85 citation statements)

References 57 publications

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“…CB1R agonists appear to have limited efficacy in promoting abstinence from cannabis ( Allsop et al, 2014 ; Levin et al, 2011 ), though nabiximols may reduce cannabis craving and anxiety associated with withdrawal. Two brief trials examining the efficacy of CBD in attenuating cannabis use also had modest results ( Freeman et al, 2020 ; Solowij et al, 2018 ). Lastly, and by far the most promising, was a trial examining the efficacy of the FAAH inhibitor PF-04457845 in the treatment of cannabis dependence ( D'Souza et al, 2019 ).…”

Section: Cannabinoid Targetsmentioning

confidence: 99%

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Doncheck

Reichel

McRae‐Clark

2021

Neurobiology of Stress

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Stress is a frequent precipitant of relapse to drug use. Pharmacotherapies targeting a diverse array of neural systems have been assayed for efficacy in attenuating stress-induced drug-seeking in both rodents and in humans, but none have shown enough evidence of utility to warrant routine use in the clinic. We posit that a critical barrier in effective translation is inattention to sex as a biological variable at all phases of the research process. In this review, we detail the neurobiological systems implicated in stress-induced relapse to cocaine, opioids, methamphetamine, and cannabis, as well as the pharmacotherapies that have been used to target these systems in rodent models, the human laboratory, and in clinical trials. In each of these areas we additionally describe the potential influences of biological sex on outcomes, and how inattention to fundamental sex differences can lead to biases during drug development that contribute to the limited success of large clinical trials. Based on these observations, we determine that of the pharmacotherapies discussed only α 2 -adrenergic receptor agonists and oxytocin have a body of research with sufficient consideration of biological sex to warrant further clinical evaluation. Pharmacotherapies that target β-adrenergic receptors, other neuroactive peptides, the hypothalamic-pituitary-adrenal axis, neuroactive steroids, and the endogenous opioid and cannabinoid systems require further assessment in females at the preclinical and human laboratory levels before progression to clinical trials can be recommended.

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Section: Cannabinoid Targetsmentioning

confidence: 99%

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Doncheck

Reichel

McRae‐Clark

2021

Neurobiology of Stress

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“…This is an important line of investigation that could not be addressed, but nonetheless warrants further assessment. Furthermore, as the data were from almost two decades ago, the potential differential impacts of cannabis potency on the risk of hypertension need further examination, given recent evidence indicating rising concentrations of delta‐9‐tetrahydrocannabinol over time [25,26]. In a similar manner, the potential differential impacts of routes of administration (i.e.…”

Section: Discussionmentioning

confidence: 99%

The longitudinal relationship between cannabis use and hypertension

Haleem

Hwang

Elton‐Marshall

et al. 2021

Drug and Alcohol Review

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Introduction The relationship between cannabis use and hypertension is not clear based on prior epidemiological studies. Thus, we examined this relationship over a 3‐year follow‐up period using a large population‐based sample from the USA. Methods Self‐reported longitudinal data were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions Wave 1 (2001/2002) and Wave 2 (2004/2005). The sample was restricted to participants who did not report hypertension at baseline (n = 26 844; 51% 40 years and older, 51% female, 71% white). χ2‐tests were used to examine the distributions of confounders stratified by the incidence of hypertension. Thereafter, multiple logistic regression analyses were conducted to quantify the relationships between lifetime cannabis use, 12‐month cannabis use and 12‐month cannabis use frequency and incidence of hypertension while adjusting for confounders. Results Cannabis use was associated with a decreased incidence of hypertension in the unadjusted analyses. However, the relationships were confounded by age. After adjustment for all confounders, neither lifetime cannabis use (odds ratio, 95% confidence interval 0.89, 0.77 to 1.02), 12‐month cannabis use (0.78, 0.56 to 1.09) nor 12‐month cannabis use frequency [at least monthly use (0.85, 0.57 to 1.28) and less than monthly use (0.67, 0.40 to 1.11)] were associated above chance with the incidence of hypertension. Discussion and Conclusions Lifetime cannabis use, 12‐month cannabis use and 12‐month cannabis use frequency were not associated with the incidence of hypertension.

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“…Patients with dual diagnosis are particularly difficult to treat and are generally afflicted by worse outcomes than patients with psychosis alone. The increasing potency of available cannabis is of global concern [ 44 , 45 ], and the results of this trial will become increasingly important.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial

et al. 2021

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Background Cannabis use is an important risk factor for development of psychosis and further transition to schizophrenia. The prevalence of patients with psychosis and comorbid cannabis use (dual diagnosis) is rising with no approved specialized pharmacological treatment option. Cannabidiol, a constituent of the Cannabis sativa plant, has potential both as an antipsychotic and as a cannabis substituting agent. The aim of this study is to evaluate the efficacy of cannabidiol versus a first-choice second-generation antipsychotic (risperidone) in patients with early psychosis and comorbid cannabis use. Methods The study is a phase II randomized, double-blinded, parallel-group, active-comparator clinical trial. We plan to include 130 patients aged between 18 and 64 years with a recent diagnosis of psychosis, comorbid cannabis use, and currently not treated with antipsychotics. The participants will be randomized to seven weeks of treatment with either cannabidiol 600 mg (300 mg BID) or risperidone 4 mg (2 mg BID). Participants will undergo clinical assessment after 1, 3, 5 and 7 weeks, telephone assessment the weeks in between, and a safety visit two weeks after end of treatment. The primary outcomes are cessation of cannabis use (self-reported) and psychotic symptom severity. The secondary outcomes include frequency and quantity of cannabis use, global illness severity, psychosocial functioning, subjective well-being, cognition, sleep, circadian rhythmicity, and metabolomics. Discussion The results of this trial can potentially contribute with a new treatment paradigm for patients suffering from dual diagnosis. Trial registration ClinicalTrials.gov, NCT04105231, registered April 23rd, 2021

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Changes in delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta‐analysis

Cited by 159 publications

References 57 publications

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

The longitudinal relationship between cannabis use and hypertension

Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial

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