Category Archives: Addiction

State marijuana laws and opioid overdose mortality.

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Image result for Injury Epidemiology “The opioid epidemic in the United States is a national public health crisis.

In recent years, marijuana legalization has been increasingly adopted by state governments as a policy intervention to control the opioid epidemic under the premise that marijuana and opioids are substitutive substances.

The purpose of this systematic review is to synthesize the empirical evidence regarding the impact of state marijuana laws on opioid overdose mortality and other opioid-related health outcomes.

RESULTS:

Of the 16 eligible studies, 4 assessed the association of state marijuana law status with opioid overdose mortality, 7 with prescription opioids dispensed, and the remaining with nonmedical use and opioid-related hospitalizations. Random effects modeling based on pooled data revealed that legalizing marijuana for medical use was associated with a statistically non-significant 8% reduction in opioid overdose mortality (95% confidence interval: - 0.21 to 0.04; p = 0.201) and a 7% reduction in prescription opioids dispensed (95% confidence interval: - 0.13 to - 0.01; p = 0.017). Legalizing marijuana for recreational use was associated with an additional 7% reduction in opioid overdose mortality in Colorado and 6% reduction in opioid prescriptions among fee-for-service Medicaid and managed care enrollees.

CONCLUSIONS:

Legalizing marijuana might contribute to a modest reduction in opioid prescriptions. Evidence about the effect of marijuana legalization on opioid overdose mortality is inconsistent and inconclusive. If any, the effectiveness of state marijuana laws in reducing opioid overdose mortality appears to be rather small and limited to states with operational marijuana dispensaries. It remains unclear whether the presumed benefit of legalizing marijuana in reducing opioid-related harms outweighs the policy’s externalities, such as its impact on mental health and traffic safety.”

https://www.ncbi.nlm.nih.gov/pubmed/31497489

“Legalizing marijuana might contribute to a modest reduction in opioid prescriptions.”

https://injepijournal.biomedcentral.com/articles/10.1186/s40621-019-0213-z

Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol may be effective against methamphetamine induced mitochondrial dysfunction and inflammation by modulation of Toll-like type-4(Toll-like 4) receptors and NF-κB signaling.

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Medical Hypotheses“The neurodegeneration, neuro-inflammation and mitochondrial dysfunction which occur by methamphetamine (METH) abuse or administration are serious and motivation therapeutic approaches for inhibition of these types of neurodegeneration. As we know, METH through Toll-like receptors (TLRs), specially type 4, and NF-κB signaling pathway causes neuro-inflammation and mitochondrial dysfunction.

Neuroprotective approach for management of METH-induced neurodegeneration, inflammation and mitochondrial dysfunction, through a novel neuroprotective agent is continuously being superior to any kind of other therapeutic strategy. Therefore, the clarification, introduction and development of efficacious novel neuroprotective agent are demanded. During recent years, using new neuroprotective agent with therapeutic probability for treatment of METH-induced neuro-inflammation and mitochondrial dysfunction has been astoundingly increased.

Previous studies have stated the neuroprotective and anti-inflammatory roles of cannabinoid derivate such as cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ9-THC) in multiple neurodegenerative events and diseases.

According to literature cannabinoid derivate, by inhibition of TLR4 and activation of NF-κB signaling pathway, exerts their anti-inflammatory and neuroprotective effects and cause mitochondrial biogenesis. Thus we hypothesized that by using cannabinoids in METH dependent subject it would provide neuroprotection against METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction and probably can manage sequels of METH-induced neurochemical abuses via modulation of TLR4/NF-κB signaling pathway.

In this article, we tried to discuss our hypothesis regarding the possible role of CBD and Δ9-THC, as a potent neuroprotective and anti-inflammatory agents, in inhibition or treatment of METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction through its effects on TLR4/NF-κB signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/31465975

https://www.sciencedirect.com/science/article/abs/pii/S030698771930739X?via%3Dihub

Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in multiple rodent models of nicotine dependence.

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British Journal of Pharmacology banner“Both types of cannabinoid receptors – CB1 and CB2 – regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs.

Δ9 -Tetrahydrocannabivarin (Δ9 -THCV) – a cannabis constituent – acts as a CB1 antagonist and a CB2 agonist. Δ8 -Tetrahydrocannabivarin (Δ8 -THCV) is a Δ9 -THCV analogue with similar combined CB1 antagonist/CB2agonist properties.

KEY RESULTS:

Δ8 -THCV significantly attenuated intravenous nicotine self-administration, and both cue-induced and nicotine-induced relapse to nicotine-seeking behavior in rats. Δ8 -THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice.

CONCLUSIONS AND IMPLICATIONS:

We conclude that Δ8 -THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/31454413

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14844

Clinicians’ Guide to Cannabidiol and Hemp Oils.

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Mayo Clinic“Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana.

In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils.

There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction.

Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities.

This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products.

We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations.

This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.”

https://www.ncbi.nlm.nih.gov/pubmed/31447137

https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext

Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH1A and TRPV1 receptor mechanisms.

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Neuropharmacology“Cocaine abuse continues to be a serious health problem worldwide. Despite intense research there is currently no FDA-approved medication to treat cocaine use disorder. The recent search has been focused on agents targeting primarily the dopamine system, while limited success has been achieved at the clinical level.

Cannabidiol (CBD) is a U.S. FDA-approved cannabinoid for the treatment of epilepsy and recently was reported to have therapeutic potential for other disorders. Here we systemically evaluated its potential utility for the treatment of cocaine addiction and explored the underlying receptor mechanisms in experimental animals.

These findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine via a DA-dependent mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/31437433

https://www.sciencedirect.com/science/article/pii/S0028390819302990?via%3Dihub

The effectiveness of self-directed medical cannabis treatment for pain

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Complementary Therapies in Medicine“The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief.

Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis’ effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was –3.10 points on a 0–10 visual analogue scale (SD = 2.16, d = 1.55, p < .001).

Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain.

These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

The results suggest that Cannabis flower with moderate to high levels of tetrahydrocannabinol is an effective mid-level analgesic.”

https://www.ncbi.nlm.nih.gov/pubmed/31519268

https://www.sciencedirect.com/science/article/abs/pii/S0965229919308040

“UNM study confirms cannabis flower is an effective mid-level analgesic medication for pain treatment. Cannabis likely has numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids, which likely act synergistically for people that use whole dried cannabis flower, Cannabis offers the average patient an effective alternative to using opioids for general use in the treatment of pain with very minimal negative side effects for most people.”  https://news.unm.edu/news/unm-study-confirms-cannabis-flower-is-an-effective-mid-level-analgesic-medication-for-pain-treatment

THE EFFECTS OF MEDICAL MARIJUANA DISPENSARIES ON ADVERSE OPIOID OUTCOMES

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 Publication cover image“As more states enact laws liberalizing marijuana use and the U.S. opioid epidemic surges to unprecedented levels, understanding the relationship between marijuana and opioids is growing increasingly important.

Using a unique self‐constructed marijuana dispensary dataset, I estimate the impact of increased marijuana access on opioid‐related harms.

I exploit within‐ and across‐state variation in dispensary openings and find county‐level prescription opioid‐related fatalities decline by 11% following the opening a dispensary.

The estimated dispensary effects are qualitatively similar for opioid‐related admissions to treatment facilities. These results are strongest for males and suggest a substitutability between marijuana and opioids.”

https://onlinelibrary.wiley.com/doi/full/10.1111/ecin.12825

“I find that core-based statistical areas (CBSAs) with dispensary openings experience a 20 percentage point relative decrease in painkiller treatment admissions over the first two years of dispensary operations.”

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3012381

“Access to medical marijuana reduces opioid prescriptions”  https://www.health.harvard.edu/blog/access-to-medical-marijuana-reduces-opioid-prescriptions-2018050914509

THE EFFECTS OF RECREATIONAL MARIJUANA LEGALIZATION AND DISPENSING ON OPIOID MORTALITY

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Publication cover image“This study documents how the changing legal status of marijuana has impacted mortality in the United States over the past two decades.

We use a difference‐in‐difference approach to estimate the effect of medical marijuana laws (MML) and recreational marijuana laws (RML) on fatalities from opioid overdoses, and we find that marijuana access induces sharp reductions in opioid mortality rates.

Our research corroborates prior findings on MMLs and offers the first causal estimates of RML impacts on opioid mortality to date, the latter of which is particularly important given that RMLs are far more expansive in scope and reach than MMLs.

In our preferred econometric specification, we estimate that RMLs reduce annual opioid mortality in the range of 20%–35%, with particularly pronounced effects for synthetic opioids. In further analysis, we demonstrate how RML impacts vary among demographic groups, shedding light on the distributional consequences of these laws.

Our findings are especially important and timely given the scale of the opioid crisis in the United States and simultaneously evolving attitudes and regulations on marijuana use.”

https://onlinelibrary.wiley.com/doi/full/10.1111/ecin.12819

“Marijuana legalization reduces opioid deaths. A new Economic Inquiry study finds that marijuana access leads to reductions in opioid-related deaths.” https://medicalxpress.com/news/2019-08-marijuana-legalization-opioid-deaths.html

Endocannabinoid System and Alcohol Abuse Disorders.

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“Δ9-tetrahydrocannabinol (Δ9-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal. CB2 receptors (CB2R) are demonstrated in microglial cells, astrocytes, and several neuron subpopulations and are present in both pre- and postsynaptic terminals.

The majority of studies on these receptors have been conducted in the past two and half decades after the identification of the molecular constituents of the endocannabinoid (eCB) system that started with the characterization of CB1R. Subsequently, the seminal discovery was made, which suggested that alcohol (ethanol) alters the eCB system, thus establishing the contribution of the eCB system in the motivation to consume ethanol. Several preclinical studies have provided evidence that CB1R significantly contributes to the motivational and reinforcing properties of ethanol and that the chronic consumption of ethanol alters eCB transmitters and CB1R expression in the brain nuclei associated with addiction pathways.

Additionally, recent seminal studies have further established the role of the eCB system in the development of ethanol-induced developmental disorders, such as fetal alcohol spectrum disorders (FASD). These results are augmented by in vitro and ex vivo studies, showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the eCB system during development and in the adult stage. This chapter provides a current and comprehensive review of the literature concerning the role of the eCB system in alcohol abuse disorders (AUD).”

https://www.ncbi.nlm.nih.gov/pubmed/31332736

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_6

“Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742761/

Cannabis Use Motivations among Adults Prescribed Opioids for Pain versus Opioid Addiction.

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Pain Management Nursing“Cannabis has been linked to reduced opioid use, although reasons for cannabis use among adults prescribed opioids are unclear.

The purpose of this study was to determine whether motivations for cannabis use differ between adults prescribed opioids for persistent pain versus those receiving opioids as medication-assisted treatment for opioid use disorder.

RESULTS:

More than half the sample (n = 122) reported current, daily cannabis use and 63% reported pain as a motivation for use. Adults with persistent pain were more likely to be older, female, and have higher levels of education (p < .05). Adults with opioid use disorder were more likely to report “enhancement” (p < .01) and relief of drug withdrawal symptoms (p < .001) as motivations for cannabis use. The most common reasons for cannabis use in both populations were social and recreational use and pain relief.

CONCLUSIONS:

Both studied populations have unmet health needs motivating them to use cannabis and commonly use cannabis for pain. Persistent pain participants were less likely to use cannabis for euphoric effects or withdrawal purposes. Nurses should assess for cannabis use, provide education on known risks and benefits, and offer options for holistic symptom management.”

https://www.ncbi.nlm.nih.gov/pubmed/31375419

https://www.painmanagementnursing.org/article/S1524-9042(19)30096-7/fulltext