The (endo)cannabinoid signaling in female reproduction: What are the latest advances?
Abstract: Cannabis extracts like marijuana have the highest consumption rate worldwide. Yet, their societal acceptance as recreational and therapeutic drugs could represent a serious hazard to female human reproduction, because cannabis ingredients [termed (phyto)cannabinoids] can perturb an endogenous system of lipid signals known as endocannabinoids. Accumulated evidence on animal models and humans has demonstrated a crucial role of these endogenous signals on different aspects of female reproduction, where they act through an ensamble of proteins that synthesize, transport, degrade and traffic them. Several reports have recently evidenced the potential role of endocannabinoids as biomarkers of female infertility for disease treatment and prevention, as well as their possible epigenetic effects on pregnancy.

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Abstract (Excerpt): As global interest in the therapeutic potential of cannabis and its’ derivatives for the management of selected diseases increases, it is increasingly imperative that the toxic profile of cannabinoids be thoroughly understood in order to correctly assess the balance between the therapeutic risks and benefits. Modern studies across a number of jurisdictions, including Canada, Australia, the US and Europe have confirmed that some of the most worrying and severe historical reports of both congenital anomalies and cancer induction following cannabis exposure actually underestimate the multisystem thousand megabase-scale transgenerational genetic damage. These findings from teratogenic and carcinogenic literature are supported by recent data showing the accelerated patterns of chronic disease and the advanced DNA methylation epigenomic clock age in cannabis exposed patients. Together, the increased multisystem carcinogenesis, teratogenesis and accelerated aging point strongly to cannabinoid-related genotoxicity being much more clinically significant than it is widely supposed and, thus, of very considerable public health and multigenerational impact.

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Jessica Nye, PhD  February 8, 2023
Study authors did not identify clear pain-relieving effects from CBD and/or THC among patients with peripheral neuropathic pain and prior treatment failure.
Oral cannabidiol (CBD), tetrahydrocannabinol (THC), or their combination did not decrease pain among patients with peripheral neuropathic pain who had a history of treatment failure. These findings, from a randomized, double-blind trial, were published in the European Journal of Pain.
The median age of the study population was 65 (range, 22-95) years, the median duration of pain was 60 (range, 10-2017) months, mean NRS score was 6.5 (standard deviation [SD], 1.3) points, and the most common prior therapy was gabapentin or pregabalin (n=115). Neuropathic etiologies included polyneuropathy (n=95), diabetic polyneuropathy
“In the PPP, CBD reduced pain less than placebo, and less effect of CBD than of placebo was also seen with some secondary pain outcomes.”
Neither CBD, THC, nor CBD/THC were superior to placebo for symptoms of burning pain, pressing and squeezing, pain paroxysms, or evoked pain as evaluated using the Neuropathic Pain Symptom Inventory (NPSI).  The study authors report that CBD was actually less effective than placebo in reducing evoked pain.
No effects on paracetamol consumption, quality of life, or psychomotor function were reported with active treatment.
In subgroup analyses, active treatment was not superior to placebo for pain, quality of life, mood, or pain-related sleep disturbance.
Nausea and diarrhea were reported more frequently among recipients of CBD/THC compared with prior to treatment (11% vs 1% and 11% vs 3%, respectively).

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Conclusions: Accurate and informative labelling of hemp and hemp-derived CBD products is an important public health issue. FDA-regulated product labels are considered an essential tool for protecting consumers and enabling informed decision-making. Untruthful or unsubstantiated health-related claims, and unallowed Drug Claims, in marketing materials and on labels of CBD products may create harm by enticing consumers to forgo more evidence-based medical interventions. Furthermore, missing or inaccurate labelling of the amount of CBD, delta-9 tetrahydrocannabinol (THC), and potentially harmful contaminants such as pesticides, naturally-occurring yeast and mold or heavy metals may result in harm and/or lack of efficacy. Manufacturers of these products may reasonably be expected to understand and adhere to FDA regulations for labelling and marketing of food, dietary supplements and drugs, both over-the-counter (OTC) and prescription, even though FDA has interpreted federal law as excluding them from these categories. As manufacturers prepare for forthcoming regulations, a better understanding of the basic framework for FDA labelling and marketing regulations for food, dietary supplements and drugs is warranted.

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Also see

• Heavy metal and phthalate contamination and labelling integrity in a large sample of commercially available cannabidiol (CBD) products
  
• FDA, FTC warn company marketing unapproved cannabidiol products
  
• FDA Says Most CBD Products May Not Be Safe, and Warns 15 Companies to Stop Selling Them
  
• What You Need to Know (And What We’re Working to Find Out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD
  
• Dr Robert L Dupont's written Testimony to the FDA Regarding the Health Impacts of CBD
  

Conclusion: This is the first characterization of the effect of cannabis exposure (CE)on the entirety of the rat sperm methylome. We identified CE-associated methylation changes across the sperm methylome, some of which persisted despite a “washout” period. Select methylation changes validated via bisulfite pyrosequencing, and genes associated with methylation changes were involved in early developmental processes. Preconception CE exposure is associated with detectable changes in offspring DNA methylation that are functionally related to changes in gene expression and cardiomegaly. These results support that paternal preconception exposure to cannabis can influence offspring outcomes.

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