Category Archives: Addiction

The effects of acute alcohol administration on circulating endocannabinoid levels in humans

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“Several lines of evidence suggest that endocannabinoid signalling may influence alcohol consumption. Preclinical studies have found that pharmacological blockade of cannabinoid receptor 1 leads to reductions in alcohol intake. Furthermore, variations in endocannabinoid metabolism between individuals may be associated with the presence and severity of alcohol use disorder. However, little is known about the acute effects of alcohol on the endocannabinoid system in humans. In this study, we evaluated the effect of acute alcohol administration on circulating endocannabinoid levels by analysing data from two highly-controlled alcohol administration experiments. In the first within-subjects experiment, 47 healthy participants were randomized to receive alcohol and placebo in a counterbalanced order. Alcohol was administered using an intravenous clamping procedure such that each participant attained a nearly identical breath alcohol concentration of 0.05%, maintained over 3 h. In the second experiment, 23 healthy participants self-administered alcohol intravenously; participants had control over their exposure throughout the paradigm. In both experiments, circulating concentrations of two endocannabinoids, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), were measured at baseline and following alcohol exposure. During the intravenous clamping procedure, acute alcohol administration reduced circulating AEA but not 2-AG levels when compared to placebo. This finding was confirmed in the self-administration paradigm, where alcohol reduced AEA levels in an exposure-dependent manner. Future studies should seek to determine whether alcohol administration has similar effects on brain endocannabinoid signalling. An improved understanding of the bidirectional relationship between endocannabinoid signalling and alcohol intake may deepen our understanding of the aetiology and repercussions of alcohol use disorder.”

https://pubmed.ncbi.nlm.nih.gov/36001429/

https://onlinelibrary.wiley.com/doi/10.1111/adb.13197

Medical Cannabis Certification Is Associated With Decreased Opiate Use in Patients With Chronic Pain: A Retrospective Cohort Study in Delaware

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Cureus Competition Winners Announced - Synaptive Medical

“Opioid medications are commonly used to treat chronic pain around the world. While these medications are quite effective at reducing pain, they can create opioid dependence and lead to further drug addiction. Long-term opioid use has significantly contributed to the “opioid epidemic” that is currently ravaging the United States, leading to opioid overdoses and unintentional deaths, particularly in Delaware.

Objective To determine if medical marijuana certification helps patients in Delaware with chronic pain reduce their opiate use.

Methods In this study, we examined individuals who were provided with legal; medical cannabis certifications in the state of Delaware between June 2018 and October 2019 and were concurrently being treated with opioid medications for chronic pain at a private pain management practice. Using a posthoc analysis, we conducted a retrospective cohort study on the individuals (n = 81) to determine if there was a decrease in their opioid use following medical cannabis certification. Opioid use was measured in morphine milligram equivalent (MME) through the Delaware prescription monitoring program (PMP) database.

Results Overall, the average change in prescribed opioid use was found to be -12.3 morphine milligram equivalent (MME) units when including all individuals (p < 0.00001). Among the included individuals with baseline opioid use, medical cannabis certification was associated with a 31.3% average decrease in opioid use (n = 63). When examining subgroups based upon pain location, individuals with neck pain displayed a 41.5% average decrease in MME (n = 27), while individuals with low back pain were observed to have a 29.4% decrease in opioid use (n = 58). Similarly, individuals with knee pain (n = 14) reduced their opioid use by 32.6%.

Conclusion The results display an association between medical cannabis certification and a decrease in opiate use among the study group individuals. This study suggests that medical cannabis use may help individuals to reduce their opiate requirements along with physician intervention. More research is needed to validate these findings with appropriate controls and verification of cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/35004055/

“The results of this study indicate that medical marijuana certification is associated with a decrease in prescription opiate use for chronic pain treatment and supports greater use of this adjunct treatment modality. Given the significance of opioid addiction in American society, any treatment or additional resource to reduce opioid overuse can aid in the multifactorial management of chronic pain. Although marijuana use causes a variety of side effects, the findings here suggest that the use of medical cannabis as an adjunct treatment for chronic pain may be beneficial to public health.”

https://www.cureus.com/articles/77114-medical-cannabis-certification-is-associated-with-decreased-opiate-use-in-patients-with-chronic-pain-a-retrospective-cohort-study-in-delaware

Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study

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The BMJ (@bmj_latest) / Twitter

“Objective: To examine county level associations between the prevalence of medical and recreational cannabis stores (referred to as dispensaries) and opioid related mortality rates.

Participants: The study used US mortality data from the Centers for Disease Control and Prevention combined with US census data and data from Weedmaps.com on storefront dispensary operations. Data were analyzed at the county level by using panel regression methods.

Main outcome measure: The main outcome measures were the log transformed, age adjusted mortality rates associated with all opioid types combined, and with subcategories of prescription opioids, heroin, and synthetic opioids other than methadone. The associations of medical dispensary and recreational dispensary counts with age adjusted mortality rates were also analyzed.

Results: County level dispensary count (natural logarithm) is negatively related to the log transformed, age adjusted mortality rate associated with all opioid types (β=-0.17, 95% confidence interval -0.23 to -0.11). According to this estimate, an increase from one to two storefront dispensaries in a county is associated with an estimated 17% reduction in all opioid related mortality rates. Dispensary count has a particularly strong negative association with deaths caused by synthetic opioids other than methadone (β=-0.21, 95% confidence interval -0.27 to -0.14), with an estimated 21% reduction in mortality rates associated with an increase from one to two dispensaries. Similar associations were found for medical versus recreational storefront dispensary counts on synthetic (non-methadone) opioid related mortality rates.

Conclusions: Higher medical and recreational storefront dispensary counts are associated with reduced opioid related death rates, particularly deaths associated with synthetic opioids such as fentanyl. While the associations documented cannot be assumed to be causal, they suggest a potential association between increased prevalence of medical and recreational cannabis dispensaries and reduced opioid related mortality rates. This study highlights the importance of considering the complex supply side of related drug markets and how this shapes opioid use and misuse.”

https://pubmed.ncbi.nlm.nih.gov/33504472/

“We studied county level associations between cannabis storefront dispensaries and opioid related mortality rates in the US between 2014 and 2018. Our study found that increased medical and recreational storefront dispensary counts are associated with reduced opioid related mortality rates during the study period. These associations appear particularly strong for deaths related to synthetic opioids such as fentanyl.”

https://www.bmj.com/content/372/bmj.m4957

Self-reported cannabis use is not associated with greater opioid use in elective hand surgery patients

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SpringerLink


“Background: The purpose of this study was to examine the influence of preoperative marijuana use on postoperative opioid use during the first three postoperative days (POD 1-3) after surgery, and on expectations of pain control, resiliency, and quality-of-life scores.

Methods: All patients presenting to a single institution undergoing elective hand or upper extremity outpatient surgery were asked to complete pre- and postoperative questionnaires. Preoperative questionnaires collected information on demographics, marijuana use, tobacco use, procedure type, self-assessed health, pain control expectations, and EuroQol-5D (EQ-5D) scores. At the first postoperative visit, patients self-reported opioid consumption from POD 1-3. Multivariate linear regression analysis was used to determine which patient characteristics were predictive of greater postoperative opioid consumption during POD 1-3.

Results: Self-reported marijuana users were younger, less healthy, and more likely to use tobacco compared to non-users. Marijuana users and non-users were comparable in their use of pain medication (including non-opioids), rates of chronic pain diagnoses, and self-reported pain tolerance. EQ-5D scores were lower in marijuana users than non-users (0.64 vs. 0.72). Marijuana users and non-users were prescribed comparable quantities of opioids during the first 14 days after surgery (176 ± 148 vs 115 ± 87). Multiple linear regression analysis revealed that lower preoperative EQ-5D scores, rather than marijuana use, were associated with increased opioid consumption during POD 1-3.

Conclusions: Preoperative marijuana use was not independently associated with increased opioid use during POD 1-3 after elective hand and upper extremity surgery; instead, an association with lower preoperative EQ-5D scores was identified.”

https://pubmed.ncbi.nlm.nih.gov/35986814/

“Given the increasing prevalence of marijuana use in the USA, it is imperative that surgeons be able to counsel their patients on the effect of marijuana use on their postoperative recovery. The effect of marijuana use on hand surgery patients certainly merits further research.”

https://link.springer.com/article/10.1007/s00590-022-03321-z

Medical Cannabis Used as an Alternative Treatment for Chronic Pain Demonstrates Reduction in Chronic Opioid Use – A Prospective Study

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Pain Physician:::::

“Background: Chronic opioid therapy (COT) has been used to treat many chronic pain conditions even with poor evidence for its long-term effectiveness. Medical cannabis has emerged with certain pain-relieving properties, which has led to questions as to its’ potential application, especially in relation to its effect on opioid use.

Objectives: This study investigates a proposed clinical context in offering medical cannabis as a treatment for chronic pain for those already using chronic opioid therapy. It then details patients’ daily morphine milligram equivalent (MME) usage.

Study design: This single-center prospective study follows a group of patients trialing medical cannabis treatment for chronic pain that is already using COT in order to determine individual efficacy. Continued medical cannabis treatment was a decision made by the patient, after trialing medical cannabis, to either continue medical cannabis along with COT at a reduced daily MME, or to revert back to their previous COT regimen.

Setting: This study was performed at the Allegheny Health Network Institute for Pain Medicine in Pittsburgh, Pennsylvania. The state of Pennsylvania legalized medical cannabis in April of 2016, and it became available to patients in February of 2018 through medical dispensaries.

Methods: One hundred and fifteen patients met the inclusion criteria, with the majority of those excluded due to not being treated with COT. Of the 115 who chose to undergo a medical cannabis trial in addition to their COT, 75 chose to remain certified for medical cannabis as they had significant pain relief and subsequently weaned down on opioids. Additionally, of the 115 choosing to undergo a medical cannabis trial, 30 chose to be decertified due to ineffectiveness or side effects, and those were placed back on their COT regimen. The other 10 were not included for other denoted reasons. Compliance was monitored through urine drug screens (UDS).

Results: There was a 67.1% average decrease in daily MME/patient from 49.9 to 16.4 MME at the first follow-up. There was a 73.3% decrease in MME at second follow-up from 49.9 to 13.3 MME with an ANOVA analysis denoting a significant difference of P < 0.0001.

Limitations: The period of follow-up presented at this point includes their first 6 months of treatment with medical cannabis and COT concomitantly.

Conclusions: Presenting medical cannabis to chronic pain patients on COT should be done in the context of a patient choice between medical cannabis WITH decrement of COT or continued current dose of COT in order to maximize effectiveness in opioid reduction as well as to limit polypharmacy concerns regarding medical cannabis. Allowing for a temporary short-term period where patients may trial medical cannabis, while concomitantly gradually weaning their COT, is also essential in determining medical cannabis’ individual effectiveness for that patient’s specific type of chronic pain, which should serve to maximize long-term opioid reduction results and hence decrease opioid-related overdose deaths.”

https://pubmed.ncbi.nlm.nih.gov/35051158/

https://www.painphysicianjournal.com/linkout?issn=&vol=25&page=E113

Mortality risk for individuals with cannabis use disorders in relation to alcohol use disorders: Results of a follow-up study

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Psychiatry Research

“Background: There are few studies on mortality on individuals entering treatment for cannabis use disorders.

Objectives: To estimate mortality risk for individuals treated for cannabis use disorders comparing patients with concomitant alcohol use disorders to those with only cannabis use disorders.

Methods: Follow-up study on 1136 residents in Northern Italy who turned to health services following problems caused by cannabis use disorders between 2009 and 2019. Individuals with concomitant use of opioids, amphetamines, cocaine, or injecting drugs were excluded. Crude mortality rates per 1000 Person Years (CMR), and standardized mortality ratios adjusted for age, sex and calendar year (SMR) were calculated.

Results: Elevated CMRs (CMR 4.4, 3-6.4), higher among patients with concomitant alcohol use disorders (CMR 10.2, 6.6-15.6) compared to those with only cannabis use disorders (CMR 1.8, 0.9-3.6) were found. Regarding excess mortality with respect to the general population, SMRs were higher and statistically significant (SMR 5.4, 3.7-7.8), both among patients with concomitant alcohol use disorders (SMR 10.2, 6.6-15.6) and among those with only cannabis use disorders (SMR 2.3, 1.1-4.5).

Conclusions: The results of this study show that individuals with only cannabis use disorders have a lower mortality risk compared to those with both cannabis and alcohol use disorders.”

https://pubmed.ncbi.nlm.nih.gov/35908347/

“The results of our study show that individuals with only cannabis use disorders have a lower mortality risk compared to those with cannabis and alcohol use disorders.”

https://www.sciencedirect.com/science/article/abs/pii/S0165178122003365?via%3Dihub

“Daily drinking is associated with increased mortality”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214719/

Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report

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SAGE Journals

“Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products.

Case summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2.

Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma.

Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis’s effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day.

Conclusion and relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.”

https://pubmed.ncbi.nlm.nih.gov/35898257/

https://journals.sagepub.com/doi/10.1177/00185787211061374

Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain: A Systematic Review

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Archive of "Cureus". - PMC

“We conducted a systematic review to determine the efficacy and safety of cannabidiol (CBD) for chronic pain.

CBD and tetrahydrocannabinol (THC), both from Cannabis plants with almost identical chemical structures, attach to the CB receptor, eliciting different effects like the psychoactivity seen on THC but less or none in CBD.

Regulations of CBD worldwide differ from each other due to the insufficiency of solid evidence to establish its benefit versus the risks. However, a few studies are showing the benefits of CBD not only for chronic pain but also for sleep improvement and quality of life.

In conclusion, CBD is an excellent alternative to an opioid in chronic pain because CBD is non-intoxicating in its pure form. More clinical trials should be done to prove CBD’s significance clinically and statistically.”

https://pubmed.ncbi.nlm.nih.gov/35860716/

“It is essential to know that pure CBD extract is a strong candidate as an alternative to opioid medication since it is nonintoxicating and dependence is less. This systematic review can benefit other researchers and even ordinary people eager to know the latest updates on CBD research on chronic pain. In the future, clinical trials should focus more on using pure CBD extract to treat chronic pain to attain evidence to properly recommend CBD in the health insurance sector so that patients may benefit to the full extent.”

https://www.cureus.com/articles/101310-efficacy-safety-and-regulation-of-cannabidiol-on-chronic-pain-a-systematic-review


Cannabinoids as Potential Molecules for Addiction Disorders

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“Addictions are a group of chronic and recurrent diseases of the brain characterized by a pathological search for reward or relief through the use of a substance or other action. This situation implies an inability to control behavior, difficulty in permanent abstinence, a compelling desire to consume, decreased recognition of significant problems caused by behavior and interpersonal relationships, and a dysfunctional emotional response. The result is a decrease in the quality of life of the affected person, generating problems in their work, academic activities, social relationships, or family or partner relationships. Unfortunately, there are not enough pharmacotherapeutic solutions to treat addictions due to the complexity of their physiopathology and signaling pathways. Therefore, it is an imperative search for new pharmacological alternatives which may be used for this purpose.

This review summarizes the main recent findings of the potential therapeutic effects of different cannabinoids on treating several addictions, including alcohol, opioids, methamphetamine, cocaine, and nicotine use disorders.

Highlights Standpoints: It has been demonstrated that many phyto, synthetic, and endogenous cannabinoids may act as therapeutic molecules in this psychiatric pathology through their action on multiple cannabinoid receptors. To highlight, cannabinoid receptors, types 1 and 2 (CB1 and CB2) have a crucial role in modulating the anti-addictive properties of these compounds.”

https://pubmed.ncbi.nlm.nih.gov/35538819/

https://www.eurekaselect.com/article/123316

Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological Characteristics of the Patient Population: A Prospective Study

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Frontiers Logo

“Background: Despite the absence of rigorous prospective studies, there has been an increase in the use of cannabis-based medicinal products. During the study period, the use of medical cannabis in Israel was tightly regulated by national policy. Through a prospective study of approximately 10,000 patients, we aimed to characterize the medical cannabis patient population as well as to identify treatment adherence, safety, and effectiveness.

Methods and findings: In this study of prescribed medical cannabis patients, adherence, safety, and effectiveness were assessed at 6 months. Treatment adherence was assessed by the proportion of patients purchasing the medication out of the total number of patients (excluding deceased cases and patients transferred to another cannabis clinic). Safety was assessed by the frequency of the side-effects, while effectiveness was defined as at least moderate improvement in the patient condition without treatment cessation or serious side-effects. The most frequent primary indications requiring therapy were cancer (49.1%), followed by non-specific pain (29.3%). The average age was 54.6 ± 20.9 years, 51.1% males; 30.2% of the patients reported prior experience with cannabis. During the study follow-up, 1,938 patients died (19.4%) and 1,735 stopped treatment (17.3%). Common side-effects, reported by 1,675 patients (34.2%), were: dizziness (8.2%), dry mouth (6.7%), increased appetite (4.7%), sleepiness (4.4%), and psychoactive effect (4.3%). Overall, 70.6% patients had treatment success at 6 months. Multivariable logistic regression analysis revealed that the following factors were associated with treatment success: cigarette smoking, prior experience with cannabis, active driving, working, and a young age. The main limitation of this study was the lack of data on safety and effectiveness of the treatment for patients who refused to undergo medical assessment even at baseline or died within the first 6 months.

Conclusions: We observed that supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events.”

https://pubmed.ncbi.nlm.nih.gov/35223923/


“This is a large study describing certain characteristics of medical cannabis users in a tightly regulated environment. The treatment appears to be safe and efficacious.”

https://www.frontiersin.org/articles/10.3389/fmed.2022.827849/full