Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic

doi:10.1016/j.tins.2016.12.006

Trends in Neurosciences

Volume 40, Issue 3, March 2017, Pages 124-127

https://doi.org/10.1016/j.tins.2016.12.006 Get rights and content

Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.

Section snippets

Curbing an Epidemic

In an unprecedented report, the US Surgeon General recently released their first state of the science on substance use, addiction, and health to fully recognize substance use and addiction as significant and substantial public health challenges [1]. As emphasized in the report, a major component of the current substance use crisis is the misuse and abuse of opioid drugs. The numbers are alarming. In the United States, approximately 2.5 million people have been diagnosed with an opioid use

The Changing Sociopolitical Pendulum of Medicinal Marijuana

The predominant pharmacological treatments currently prescribed for OUDs are methadone, buprenorphine, and naltrexone, which directly target the opioid system. These medications have been of significant clinical value but also have their own challenges (often associated with strict governmental regulations governing their use). One emerging solution showing potential therapeutic properties is cannabinoids. States with legalized marijuana laws have reported a reduction in opioid use, as

Making the Case for CBD As a Treatment for Opioid Addiction

There is a strong scientific basis for considering CBD as a therapeutic intervention for OUDs. First, in contrast to most current opioid medications, there is minimal concern about diversion to the black market. In contrast to Δ⁹-tetrahydrocannabinol (THC), the prominent psychoactive component of marijuana, CBD is not rewarding 3, 4 and as such has limited misuse and diversion potential. In addition, CBD has very low lethality, thus alleviating concerns about potential overdose. Moreover, when

CBD to Treat Opioid Addiction: Neurobiological Considerations

The endogenous cannabinoid [endocannabinoid (eCB)] system has been well documented to contribute to the stress responsivity and negative emotional states that dominate substance use disorders [8]. The eCB system is composed of G-protein-coupled receptors, including the cannabinoid receptor type 1 (CB1R) (prominent subtype expressed in the central nervous system) and CB2R (mainly expressed in the periphery); small neuromodulatory lipid ligands [N-arachidonylethanolamide (anandamide; AEA) and

The Crosstalk between CBD and Opioid Addiction

What initially made a cannabinoid strategy intriguing to consider for opiate addiction is the tight crosstalk and often reciprocal interactions that exist between the endogenous opioid and eCB systems. For example, (i) animals deficient in CB1R have reduced opioid reward, (ii) opioids regulate the release of eCBs and eCBs alter opioid peptide levels, (iii) eCB and opioid receptors are expressed in the same cells in discrete neuronal pathways highly implicated in addiction, and (iv) because they

Concluding Remarks … So Where Do We Go from Here?

It is important to move with a deep sense of urgency to leverage the opportunity presented by increased legalization of medical marijuana to expedite the development of CBD for therapeutic interventions for OUDs, thus curbing the opioid epidemic. Clinical trials must be of the highest priority to establish the most appropriate formulations, entourage effects with other cannabinoids, routes of administration, and treatment regimens for the use of CBD by individuals with OUDs. Although

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Cannabidiol induces systemic analgesia through activation of the PI3Kγ/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism
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Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia. Methods: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice. Results: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception. Conclusion: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of K_ATP channels on peripheral nociceptors.
Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis
2023, International Journal of Drug Policy
Accumulating evidence has indicated that cannabis substitution is often used as a harm reduction strategy among people who use unregulated opioids (PWUO) and people living with chronic pain. We sought to investigate the association between cannabis use to manage opioid cravings and self-reported changes in opioid use among structurally marginalized PWUO.
The data were collected from a cross-sectional questionnaire administered to PWUO in Vancouver, Canada. Binary logistic regression was used to analyze the association between cannabis use to manage opioid cravings and self-reported changes in unregulated opioid use.
A total of 205 people who use cannabis and opioids were enrolled in the present study from December 2019 to November 2021. Cannabis use to manage opioid cravings was reported by 118 (57.6%) participants. In the multivariable analysis, cannabis use to manage opioid cravings (adjusted Odds Ratio [aOR] = 2.13, 95% confidence interval [CI]: 1.07, 4.27) was significantly associated with self-reported reductions in opioid use. In the sub-analyses of pain, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among people living with moderate to severe pain (aOR = 4.44, 95% CI: 1.52, 12.97). In the sub-analyses of males and females, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among females (aOR = 8.19, 95% CI: 1.20, 55.81).
These findings indicate that cannabis use to manage opioid cravings is a prevalent motivation for cannabis use among PWUO and is associated with self-assessed reductions in opioid use during periods of cannabis use. Increasing the accessibility of cannabis products for therapeutic use may be a useful supplementary strategy to mitigate exposure to unregulated opioids and associated harm during the ongoing drug toxicity crisis.
High-CBD Cannabis Vapor Attenuates Opioid Reward and Partially Modulates Nociception in Female Rats
2023, Addiction Neuroscience
Chronic pain patients report analgesic effects when using cannabidiol (CBD), a phytocannabinoid found in whole-plant cannabis extract (WPE). Several studies suggest that cannabis-derived products may serve as an analgesic adjunct or alternative to opioids, and importantly, CBD may also attenuate the abuse potential of opioids. Vaping is a popular route of administration among people who use cannabis, however both the therapeutic and hazardous effects of vaping are poorly characterized. Despite the fact that chronic pain is more prevalent in women, the ability of inhaled high-CBD WPE to relieve pain and reduce opioid reward has not been studied in females. Here, we present a comprehensive analysis of high-CBD WPE vapor inhalation in female rats. We found that WPE was modestly efficacious in reversing neuropathy-induced cold allodynia in rats with spared nerve injury (SNI). Chronic exposure to WPE did not affect lung cytoarchitecture or estrous cycle, and it did not induce cognitive impairment, social withdrawal or anxiolytic effects. WPE inhalation prevented morphine-induced conditioned place preference and reinstatement. Similarly, WPE exposure reduced fentanyl self-administration in rats with and without neuropathic pain. We also found that WPE vapor lacks of reinforcing effects compared to the standard excipient used in most vapor administration research. Combined, these results suggest that although high-CBD vapor has modest analgesic effects, it has a robust safety profile, no abuse potential, and it significantly reduces opioid reward in females. Clinical studies examining high-CBD WPE as an adjunct treatment during opioid use disorder are highly warranted.
Cannabidiol and substance use disorder: Dream or reality
2022, Neuropharmacology
Citation Excerpt :
As a whole plant, Cannabis L. sativa (cannabis) comprises various non-psychotomimetic and non-addictive constituents that, taken in isolation, present medical opportunities and maybe more easily employed for use in medical applications (Hurd, 2017). Cannabidiol (CBD), the most abundant phytocannabinoid of cannabis after Δ9-tetrahydrocannabinol (THC), has generated significant hope in treating drug addiction (Calpe-López et al., 2019; Chye et al., 2019; Hurd, 2017). In the past two decades, a large body of basic and clinical research has revealed that CBD can be beneficial for treating neurological disorders such as epilepsy (Devinsky et al., 2014; Samanta, 2019), multiple sclerosis (Kozela et al., 2011), Parkinson's disease (Chagas et al., 2014; Zuardi et al., 2009), and Alzheimer's disease (Cheng et al., 2014; Martín-Moreno et al., 2011).
Cannabidiol (CBD) is one of the major constituents of Cannabis sativa L. that lacks psychotomimetic and rewarding properties and inhibits the rewarding and reinforcing effects of addictive drugs such as cocaine, methamphetamine (METH), and morphine. Additionally, CBD's safety profile and therapeutic potential are currently evaluated in several medical conditions, including pain, depression, movement disorders, epilepsy, multiple sclerosis, Alzheimer's disease, ischemia, and substance use disorder. There is no effective treatment for substance use disorders such as addiction, and this review aims to describe preclinical and clinical investigations into the effects of CBD in various models of opioid, psychostimulant, cannabis, alcohol, and nicotine abuse. Furthermore, the possible mechanisms underlying the therapeutic potential of CBD on drug abuse disorders are reviewed.
The current review considers and summarizes the preclinical and clinical investigations into CBD's effects in various models of drug abuse include opioids, psychostimulants, cannabis, alcohol, and nicotine.
Several preclinical and clinical studies have proposed that CBD may be a reliable agent to inhibit the reinforcing and rewarding impact of drugs.
While the currently available evidence converges to suggest that CBD could effectively reduce the rewarding and reinforcing effects of addictive drugs, more preclinical and clinical studies are needed before CBD can be added to the therapeutic arsenal for treating addiction.
Cannabidiol (CBD) reduces cocaine-environment memory in mice
2020, Pharmacology Biochemistry and Behavior
Cocaine addiction is a global health problem with no approved pharmacotherapies. Preclinical research indicates the non-intoxicating phytocannabinoid, cannabidiol (CBD), can reduce addiction-relevant behaviour for several drug classes (e.g. ethanol, opiates, psychostimulants) in rodents. However, research into the effects of CBD on cocaine addiction-like behaviours is limited, and the acute effects of CBD on cocaine reward are unknown.
The present experiments sought to clarify the effects of CBD (10 mg/kg) on the acquisition, consolidation, reconsolidation, extinction and drug-primed reinstatement of cocaine (15 mg/kg) conditioned place preference (CPP) in adult male C57BL6/J mice.
In five separate experiments, CBD was administered 1) prior to cocaine-context pairings, to target acquisition of cocaine-context memory; 2) immediately after cocaine-context pairings, to target consolidation of cocaine-context memory; 3) after a brief reactivation session, to target reconsolidation of cocaine memory; 4) prior to extinction sessions; and 5) prior to cocaine-primed reinstatement.
CBD treatment reduced preference for the cocaine-context 20 days after CBD cessation. CBD also reduced consolidation of cocaine memory, and this was evident 1 day after cessation of CBD treatment. Interestingly, CBD treatment also modified cocaine-induced locomotion. CBD did not affect reconsolidation of cocaine-induced place preference, the rate of extinction of cocaine memory, or drug-primed reinstatement of cocaine CPP.
These findings indicate specific effects of acute 10 mg/kg CBD on cocaine memory processes, suggesting delayed effects on cocaine preference and consolidation of cocaine memory, and support the therapeutic utility of CBD for targeting some drug-associated memory processes.
An Overview of Cannabidiol
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Trends in Neurosciences

Science & SocietyCannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic

Section snippets

Curbing an Epidemic

The Changing Sociopolitical Pendulum of Medicinal Marijuana

Making the Case for CBD As a Treatment for Opioid Addiction

CBD to Treat Opioid Addiction: Neurobiological Considerations

The Crosstalk between CBD and Opioid Addiction

Concluding Remarks … So Where Do We Go from Here?

Drug Alcohol. Depend.

Lancet Neurol.

Neurotherapeutics

Pharmacol. Res.

Neuropharmacology

Neurotherapeutics

Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health

Science & Society
Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic