Chronic Pain Associated With Increased Cannabis Use and Adverse Effects Among Young Adults

Nonmedical cannabis use is on this rise in adults suffering from pain, despite evidence demonstrating negative clinical outcomes. Researchers investigated the relationship between cannabis use, adverse consequences, and chronic pain in a US-based cohort of young adults aged 18–25 years.

• The sample of 403 young adults reported a mean cannabis use of 47 days in the prior 90 days; of this sample, 20 percent reported chronic pain.
• Participants with chronic pain used cannabis at significantly greater frequency (incident rate ratio [IRR], 1.35), intensity (IRR, 1.61), and reported more negative consequences (IRR, 1.23), compared with those without chronic pain.

Comments: This study contributes to a growing body of evidence that young people with chronic pain have increased cannabis use compared with their peers and experience more adverse effects. Youth are neuro-developmentally vulnerable to cannabis’s effects, with brain maturation occurring through the mid-twenties. Cultural messages that promote cannabis as a “medication” appear to be drowning out accurate information about the risks of use for this age group. Given the implications, young adults should be advised of non-cannabis alternatives to mitigate chronic pain.

(Source: Boston Medical Centre, Emily Nields, DO)

Introduction: The increase of cannabis use, particularly with the evolution of high potency products, and of cannabis use disorder (CUD) are a growing health care concern. While the harms of adult use and potential medicinal properties of cannabis continue to be debated, it is becoming evident that adolescent cannabis use is a critical window for CUD risk with potential lifelong mental health implications. Herein, we discuss mental health consequences of adolescent cannabis use, factors that contribute to the risk of developing CUD, and w(S(hat remains unclear in the changing legal landscape of cannabis use. We also discuss the importance of preclinical models to provide translational insight about the causal relationship of cannabis to CUD-related phenotypes and conclude by highlighting opportunities for clinicians and allied professionals to engage in addressing adolescent cannabis use.

Conclusion: The relationship between developmental cannabis, the impact of high potency products, and increased risk of developing CUD and mental health problems must be taken seriously, especially in light of the current mental health crisis. The plasticity of the developing brain offers windows of opportunity for prevention and early intervention to change that trajectory. Clearly new treatment strategies are needed to address the mounting challenge of CUD risk in teens and young adults. While data accumulated over the past decades about the effects of now “low dose” THC has been very valuable, significant research efforts in preclinical models are needed, focused on THC potency relevant to today’s products. Additionally, longitudinal studies such as ABCD should be able to provide important insights about factors related to resilience that may also help guide the development of intervention strategies. Altogether, the combined longitudinal, clinical and preclinical efforts will help provide unprecedented knowledge to mitigate the trajectory of CUD and related psychiatric disorders, both of which have a strong neurodevelopmental etiology.

(Source: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20231006

Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes

Abstract

Background: With the growing availability of cannabis and the popularization of additional routes of cannabis use beyond smoking, including edibles, the prevalence of cannabis use in pregnancy is rapidly increasing. However, the potential effects of prenatal cannabis use on fetal developmental programming remain unknown.

Results: We designed this study to determine whether the use of edible cannabis during pregnancy is deleterious to the fetal and placental epigenome. Pregnant rhesus macaques consumed a daily edible containing either delta-9-tetrahydrocannabinol (THC) (2.5 mg/7 kg/day) or placebo. DNA methylation was measured in 5 tissues collected at cesarean delivery (placenta, lung, cerebellum, prefrontal cortex, and right ventricle of the heart) using the Illumina MethylationEPIC platform and filtering for probes previously validated in rhesus macaque. In utero exposure to THC was associated with differential methylation at 581 CpGs, with 573 (98%) identified in placenta. Loci differentially methylated with THC were enriched for candidate autism spectrum disorder (ASD) genes from the Simons Foundation Autism Research Initiative (SFARI) database in all tissues. The placenta demonstrated greatest SFARI gene enrichment, including genes differentially methylated in placentas from a prospective ASD study.

Conclusions:  Overall, our findings reveal that prenatal THC exposure alters placental and fetal DNA methylation at genes involved in neurobehavioral development that may influence longer-term offspring outcomes. The data from this study add to the limited existing literature to help guide patient counseling and public health polices focused on prenatal cannabis use in the future.

(Source: Clinical Epigenetics Journal)

Also see

• Maternal cannabis use in pregnancy and child neurodevelopmental outcomes
• Effect of Cannabis Legalization on US Autism Incidence and Medium
• Gene linked to autism undergoes changes in men's sperm after pot use

In addition to its acute effects, cannabis/THC induces epigenetic modifications, which can affect its consumers and their offspring.

https://doi.org/10.1016/j.banm.2024.02.009

Summary: Epigenetics causes changes in the phenotype in the absence of changes in the DNA of genes, i.e., the genotype. Under various influences, such as exposure to certain xenobiotics, epigenetic marks are produced by different mechanisms, including the grafting of methyl groups onto certain cytosines of DNA, or on diaminated acids of histones, or the grafting of acetyl groups onto these histones around which the DNA of genes is wrapped. These modifications affect the exposure of these DNA segments to RNA polymerases that copy it into messenger RNAs, resulting in the carrier proteins of each of our traits. As a result, the expression of these genes can be repressed or increased. Tetrahydrocannabinol/THC, the major psychotropic and addictive principle of cannabis, induces epigenetic effects in its users that can have a lasting effect on some of their characteristics. If they are of childbearing age or if they are pregnant women, they will be able to pass on these epigenetic marks to their offspring. This transmission may result in malformations of the conceived child, reductions in height and birth weight, delayed development of staturoweight and mental health, increased risk of sudden death, hyperactivity with attention deficit, vulnerability to autism, drug addiction, depressive disorders, schizophrenia, cognitive disorders, etc. immune deficiencies.

(Source: Bulletin of the National Academy of Medicine Volume 208, Issue 4, April 2024, Pages 459-465 as publish in Science Direct)

CBD is now a widely sold supplement in oils, vapes, weed gummies, and drinks at local supermarkets

Trendy cannabidiol products such as CBD gummies and oils are a waste of money and even potentially harmful, according to Oxford scientists.

Researchers analysed 16 clinical trials and found that in 15 of them, the use of CBD was no better than a placebo at alleviating pain.

CBD is one of the chemicals found in the cannabis plant and is now a widely sold supplement in oils, vapes, weed gummies, and drinks at local supermarkets.

A highly-critical meta-analysis of existing studies around CBD by experts from the universities of Bath, Oxford, and Alberta, Canada, found there was “no evidence” the supplement worked, regardless of the dosage, how often it was taken or the route it was administered.

The report says: “For people living with pain, the evidence for CBD or hemp extract shows it is expensive, does not work, and is possibly harmful.”

The report found differing levels of CBD in products than what had been advertised, with none present in some cases.

Chemicals other than CBD were also present in some products, including tetrahydrocannabinol (THC), which is the main psychoactive part of the plant that is used recreationally and is illegal in the UK and other countries.

Experts also linked the use of CBD to increased rates of serious harm to users, including liver toxicity and hepatitis.

The products are not regulated by a medical body, and are freely available in the UK, promote health benefits including alleviating pain.

Dr Andrew Moore, co-author and former senior pain researcher at the University of Oxford, said: “For too many people with chronic pain, there’s no medicine that manages their pain. Chronic pain can be awful, so they are very motivated to find pain relief by any means. This makes them vulnerable to the wild promises made about CBD.”

He said there were “no consumer protections” and that without regulation of CBD sellers and products, it was “unlikely that the false promises being made about the analgesic effects of CBD will slow down in the years ahead”. (for complete article got to TELEGRAPH) 

Also see 

• NICE will not recommend medical cannabis for epilepsy and chronic pain
• Academic concerns around Cannabis and Pain Management