Is Cannabis the Antidote for Accutane?
Introduction
My limited understanding of how isotretinoin (Accutane) functions has allowed me to hypothesise that it causes ED/Sexual Dysfunction via a multi-faceted approach. This includes structural brain changes, 5-alpha reductase type I inhibition and the lasting effects explained through its epigenetic effects as explained in my other research document.
I have found individuals who took isotretinoin as far back as the 80’s when it was first released as an acne treatment who still suffer persistent ED/sexual dysfunction to this day. However, I have also found a small group of individuals scattered throughout the forums online who seemed to recover after suffering for a long time. I questioned them thoroughly, enquiring into their lifestyle, diet, medication history, exercise habits, recreational drug habits, etc. etc. The ONLY similarity between them all was a copious consumption of the popular illicit recreational drug cannabis. I found this intriguing and as such read if cannabinoids could affect human physiology in a counteractive way compared to isotretinoin. What I found is suggestive that it may in fact have some very positive effects.
Cannabinoids & Neurogenesis
Shohami, E., Cohen‐Yeshurun, A., Magid, L., Algali, M., & Mechoulam, R. (2011). Endocannabinoids and traumatic brain injury. British journal of pharmacology, 163(7), 1402-1410.
• There is a large body of evidence showing that the endocannabinoid (eCB) system are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain’s compensatory or repair mechanisms.
• This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies.
Steiner, M. A., & Wotjak, C. T. (2008). Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis. Progress in brain research, 170, 397-432.
• The endocannabinoid system has been recognized as a major neuromodulatory system, which functions to maintain brain homoeostasis.
Rubio-Araiz, A., Arévalo-Martín, Á., Gómez-Torres, O., Navarro-Galve, B., García-Ovejero, D., Suetterlin, P., … & Molina-Holgado, F. (2008). The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation. Molecular and Cellular Neuroscience, 38(3), 374-380.
• Found that CB1 or CB2 agonists induce neural stem cell (NSC) proliferation coupled to a significant increase in both TACE/ADAM 17 and TNF-α levels. Overall these data suggest a novel mode of action for the endocannabinoid system in NSC proliferation that is coupled to TNF signalling and that may be of therapeutic interest in the emerging field of brain repair.
Gowran, A., Noonan, J., & Campbell, V. A. (2011). The multiplicity of action of cannabinoids: implications for treating neurodegeneration. CNS neuroscience & therapeutics, 17(6), 637-644.
• The CB system is emerging as a key regulator of neuronal cell fate and is capable of conferring neuroprotection by the direct engagement of prosurvival pathways and the control of neurogenesis.
• treatment of certain neurological diseases that feature a neurodegenerative component.
Kim, S. H., Won, S. J., Mao, X. O., Ledent, C., Jin, K., & Greenberg, D. A. (2006). Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis. Journal of Pharmacology and Experimental Therapeutics, 319(1), 150-154.
• Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R.
Fernández-López, D., Lizasoain, I., Moro, M. Á., & Martínez-Orgado, J. (2013). Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury. Brain Sciences, 3(3), 1043-1059.
• The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species. Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies.
Oudin, M. J., Hobbs, C., & Doherty, P. (2011). DAGL‐dependent endocannabinoid signalling: roles in axonal pathfinding, synaptic plasticity and adult neurogenesis. European Journal of Neuroscience, 34(10), 1634-1646.
• control of adult neurogenesis in the hippocampus and subventricular zone.
Cannabinoids, 5-Alpha Reductase & Sex Hormones
PUROHIT, V., SINGH, H. H., & AHLUWALIA, B. S. (1979). Evidence that the effects of methadone and marihuana on male reproductive organs are mediated at different sites in rats. Biology of reproduction, 20(5), 1039-1044.
• The results of the study show that methadone, Δ9-THC, or CBN treatment significantly decreased (P<0.01) testosterone and DHT.
Grobin, A. C., VanDoren, M. J., Porrino, L. J., & Morrow, A. L. (2005). Cortical 3α-hydroxy-5α-pregnan-20-one levels after acute administration of Δ9-tetrahydrocannabinol, cocaine and morphine. Psychopharmacology, 179(3), 544-550.
• Δ9-THC (5 mg/kg, IP) elevated cortical allopregnanolone levels to pharmacologically active levels
• Allopregnanolone is a product of 5-alpha reductase
Epigenetics
Epigenetic control of neurogenesis by the brain endocannabinoid system: Involvement of mitogen-activated protein kinases - Francisco Molina-Holgado1, Pranali Pose1, Catherine Kollikho1, Daniel Garcia-Ovejero2, Uyen Le2, Eduardo Molina-Holgado2. 1Department of Life Sciences, University of Roehampton, London SW15 4JD, UK, 2Laboratory of Neuroinflammation, Unidad de Neurologia Experimental, Hospital Nacional de Parapléjicos, 45071 Toledo, Spain
• Emerging evidence suggests that cannabinoid signaling regulates gene expression by inducing epigenetic modification such as DNA methylation or histone modification in the regulation of a range of neurobiological processes in the brain, including CNS development, learning, memory and neurodegeneration associated with ageing.
• These studies therefore indicate a novel mode of epigenetic modification for the endocannabinoid system in neurogenesis that may be of therapeutic interest in the emerging field of brain repair.
D’Addario, C., Di Francesco, A., Pucci, M., Finazzi Agrò, A., & Maccarrone, M. (2013). Epigenetic mechanisms and endocannabinoid signalling. FEBS Journal,280(9), 1905-1917.
• The endocannabinoid system, composed of endogenous lipids, their target receptors and metabolic enzymes, has been implicated in multiple biological functions in health and disease, both in the central nervous system and in peripheral organs.
• Possibility of an ‘epigenetic therapy’ that could possibly be applied also to endocannabinoids
Conclusion
I myself have found that ‘vapourising’ cannabis on a regular basis to greatly improve my symptoms alongside a few others at this moment in time. At my worst I was almost completely impotent with drastically reduced sensitivity of the penile tissue and no libido. Within a week of vapourising my libido was enhanced to close to pre-isotretinoin levels and my erectile capacity also largely improved. However, as of yet no large improvements in sensitivity have occurred.
An interesting factor and it is why I included the study that showed decreased T & DHT is that while I’m ‘high’ it is like I’m right back at square one. No libido, impotence and for whatever reason almost complete lack of a cremastic reflex (which was also reduced after isotretinoin treatment). I seem to experience a ‘rebound effect’ the next day that last for a couple of weeks once the high sensation wears off.
So far I can only hypothesise how this works, but I believe there to be a 2-part process. A fast and slow process. The fast process is a simple ‘rebound’ from the lowered T & DHT which I presume causes a short term up-regulation in sensitivity of 5AR and other androgen receptors. The slow process involves a gradual epigenetic shift back to baseline as opposed to the epigenetic anomalies that isotretinoin may induce.
