A naturalistic examination of the perceived effects of cannabis on negative affect

Cuttler, Carrie; Spradlin, Alexander; McLaughlin, Ryan J.

doi:10.1016/j.jad.2018.04.054

Cited by 90 publications

(75 citation statements)

References 30 publications

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“…Because the dose of cannabinoids and phytochemical makeup of whole-plant cannabis have significant impacts on physiological responses (such as tachycardia) and subjective experiences (such as anxiety), additional research is needed to characterize maximally efficacious treatment protocols. 116 , 157 When used to treat opioid withdrawal symptoms, undesirable side effects also occur in a dose-dependent manner for the FDA-approved cannabinoid dronabinol. 113 The homogenous and consistent formulation of this pharmaceutical combined with the logistical ease of prescribing the drug may make it more feasible than whole-plant cannabis for clinical trials on cannabinoid alleviation of opioid withdrawal symptoms and relapse prevention.…”

Section: Shortcomings Of Cannabis In Medication-assisted Therapymentioning

confidence: 99%

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

Wiese

Wilson-Poe

2018

Cannabis and Cannabinoid Research

127

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Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive.Discussion: Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access. To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis' potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse.Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD.

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Section: Shortcomings Of Cannabis In Medication-assisted Therapymentioning

confidence: 99%

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

Wiese

Wilson-Poe

2018

Cannabis and Cannabinoid Research

127

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“…In a recent meta-analysis, cannabinoids versus comparator groups had nearly three times the odds of psychiatric or nervous system disorder side effects when studied as a combined endpoint, while individual symptoms (e.g., anxiety, depression) were not statistically significant [44]. In a recent study of medical use, cannabis was shown to reduce neuropsychiatric conditions (i.e., depression, anxiety, and stress) in the short term, while exacerbating depression over long-term use [45]. Nevertheless, FDA labeling recommends screening patients prior to initiating therapy with THC, and this is a recommendation that should be extrapolated to initiation of medical cannabis regimens [25,26].…”

Section: Neuropsychiatric Side Effectsmentioning

confidence: 97%

Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions

Brown

2020

JCM

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Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.

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“…One potential explanation for this increased behavioral efficiency is that CB 1 R agonism attenuates the aversive emotional state associated with impending punishment. Systemic CB 1 R activation in humans has been associated with attenuated anxiety and stress, and produces anti-fear effects (Rabinak et al, 2013;Childs et al, 2017;Cuttler et al, 2018), and complementary data from rodent models demonstrate that CB 1 R agonist treatments have been associated with reduced aversive learning, impaired fear memory acquisition, enhanced fear extinction learning, reduced stress responsivity, and anxiolysis (Kangarlu-Haghighi et al, 2015;Simone et al, 2015;Nasehi et al, 2016;Fokos and Panagis, 2010;Gobira et al, 2013;Kangarlu-Haghighi et al, 2015;Kinden and Zhang, 2015;Schreiber et al, 2018;Uttl et al, 2018). Interestingly, the suppressive effects of cannabinoids on anxiety, fear, and stress appear to stem from CB 1 R activation in the basolateral amygdala (BLA), which is also involved in the integration of information regarding risk of punishment and reward value (Ganon-Elazar and Akirav, 2009;Orsini et al, 2015b;Morena et al, 2016).…”

Section: Direct Cb 1 R Activation Reduces Risky Choice Latencymentioning

confidence: 99%

Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making

Freels

Liley

Gabriel

et al. 2020

Preprint

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Recent changes in policy regarding cannabis in the U.S. have been accompanied by an increase in the prevalence of cannabis use and a reduction in the perceived harms associated with consumption. However, little is understood regarding the effects of cannabinoids on cognitive processes. Given that deficient risk-taking is commonly observed in individuals suffering from substance use disorders (SUDs), we assessed the impact of manipulating cannabinoid type 1 receptors (CB 1 Rs; the primary target for ∆ 9 -tetrahydrocannabinol in the brain) on punishment-based risk-taking using the risky decision-making task (RDT) in male Long-Evans rats. The RDT measures preference for small, safe rewards over large, risky rewards associated with an escalating chance of foot shock. Systemic bidirectional CB 1 R manipulation with a CB 1 R agonist, CB 1 R antagonist, and FAAH inhibitor (which increases overall endocannabinoid tone) did not alter overt risk-taking in the RDT. Interestingly, direct CB 1 R agonism, but not indirect CB 1 R stimulation or CB 1 R blockade, resulted in reduction in latency to make risky choices while not altering safe choice latency. Our findings suggest that CB 1 R activation expedites engagement in punishment based risk-taking without affecting overall preference for risky vs. safe options. This indicates that risk preference and rate of deliberation for risk-taking are influenced by distinct neural substrates, an important consideration for development of precise treatments targeting the aberrant risk-taking typical of SUD symptomology.

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A naturalistic examination of the perceived effects of cannabis on negative affect

Abstract: Cannabis reduces perceived symptoms of negative affect in the short-term, but continued use may exacerbate baseline symptoms of depression over time.

Cited by 90 publications

References 30 publications

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions

Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making

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