Khaled Mahmoud

 Report on Cannabis Contents: Introduction Relation between cannabis and psychosis Mechanism of action for CBD References Researcher / Khaled Mahmoud Introduction: Cannabis, (genus Cannabis), plant belonging to the family Cannabaceae of the nettle order (Urticales). By some classifications, the genus Cannabis comprises a single species, hemp (Cannabis sativa), a stout, aromatic, erect annual herb that originated in Central Asia and is now cultivated worldwide, including in Europe, southern Asia, the Middle East, India, Africa, and the Americas. A tall canelike variety is raised to produce hemp fibre, while the female plant of a short branchier variety is prized as the more abundant source of the psychoactive substance tetrahydrocannabinol (THC), the active ingredient of marijuana. Delta-9-Tetrahydrocannabinol or (THC) is a psychoactive cannabinoid responsible for many of the effects experienced by the cannabis user. Mild to moderate pain relief, relaxation, insomnia and appetite stimulation. THC has been demonstrated to have anti-depressant effects. Most of strains range from 12-21% THC with very potent and carefully prepared strains reaching even higher. Recent research that suggests patients with a pre-disposition to schizophrenia and anxiety disorders should avoid high-THC cannabis. Cannabidiol or (CBD) occurs in many strains, at low levels, <1%.  In rare cases, CBD can be the dominant cannabinoid, as high as 15% by weight. Popular CBD-rich strains (>4% CBD) include Sour Tsunami, Harlequin and Cannatonic. It can provide relief for chronic pain due to muscle spasticity, convulsions and inflammation.  Offering relief for patients with MS, Fibromyalgia and Epilepsy. Some researchers feel it provides effective relief from anxiety-related disorders. CBD has also been shown to inhibit cancer cell growth when injected into breast and brain tumors in combination with THC.1 Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. An elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms.2 Relation between cannabis and psychosis: Regular cannabis use predicts an increased risk of schizophrenia, and the relationship persists after controlling for confounding variables. The relationship is unlikely to be explained by self‐medication. There is increasing evidence that the association is biologically plausible, but given the complex nature of the etiology of schizophrenia and related disorders, it is unlikely that the relationship will be due to an interaction between cannabis use and a single gene. Uncertainty about the biological mechanisms should not distract us from using educational, psychological and social interventions to reduce the use of cannabis by vulnerable young people and thereby the risk of problems related to its use.3 There is good evidence that both genetic and environmental factors are implicated in psychosis but the precise identity of these is unclear. Cannabis use is one candidate as a possible, modifiable environmental influence on both incidence and prognosis of psychosis. Evidence supporting this candidature is exclusively observational, and its strength has perhaps been overestimated and problems related to its interpretation underestimated by some. Nevertheless, the possibility that cannabis does cause psychosis remains.4 Early cannabis use is associated with psychosis-related outcomes in young adults. The use of sibling pairs reduces the likelihood that unmeasured confounding explains these findings. This study5 provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults Research suggests that on average there is a 10% to 12% likelihood of developing a psychotic disorder solely based on being at familial high risk.6 There is a possibility that clinical high risk (CHR) familial history (FH) individuals believe that it is more difficult for them to cope with circumstances such as abuse or potential abuse. Future research on this subject should investigate family environment and its role in conversion to psychosis among CHR + FH individuals.6 Epidemiological findings suggest that cannabis use is a risk factor for the emergence of psychosis, and that the induction of psychotic symptoms in the context of cannabis use may be associated with a pre-existing vulnerability for psychosis. This study investigated in a non-clinical population the interaction between cannabis use and psychosis vulnerability in their effects on psychotic experiences in daily life.7 Cannabis use interacts with psychosis vulnerability in their effects on experience of psychosis in daily life. The public health impact of the widespread use of cannabis may be considerable.7 A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system. Modulation of this system by the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia.8 Table 1.9 Prospective Studies Examining Associations Between Cannabis Use and Psychosis Outcomes Reference  Study Design (age at baseline)  Subjects (n)  Definition of Cannabis Use  Outcome  Odds Ratio (95% CI)  Adjustment  Zammit, Allebeck, Andreasson, Lundberg, & Lewis, 2002  conscript cohort (18–20 years)  50,053  lifetime use of cannabis > 50 times at baseline  schizophrenia  3.1 (95% CI: 1.7–5.5)  diagnosis at baseline, IQ, social integration, disturbed behavior, cigarette smoking, place of upbringing  Van Os, Bak, Hanssen, Bijl, de Graaf, & Verdoux, 2002  population based (18–64 years)  4,045  lifetime use of cannabis at baseline  psychotic symptoms  2.8 (95% CI: 1.2–6.5)  age, sex, ethnic group, single marital status, level of education, urbanicity, discrimination  Weiser, Knobler, Noy, & Kaplan, 2002  population based (16–17 years)  50,413  lifetime use of any drugs (principally marijuana) at baseline  schizophrenia  2.0 (95% CI: 1.3–3.1)  IQ, social functioning, nonpsychotic disorder  Arseneault, Cannon, Poulton, Murray, Caspi, & Moffitt, 2002  birth cohort (15–18 years)  759  lifetime use of cannabis by age 15  schizophreniform disorder  3.1 (95% CI: 0.7–13.3)  sex, social class, psychotic symptoms prior to cannabis use  Fergusson, Horwood, & Swain-Campbell, 2003  birth cohort (18–21 years)  1,011  DSM-IV cannabis dependence at baseline  psychotic symptoms  1.8 (95% CI: 1.2–2.6)  preceding psychotic symptoms; use of other substances; mental health; social, family, and individual factors  Stefanis, Delespaul, Henquet, Bakoula, Stefanis, & Van Os, 2004  birth cohort (19 years)  3,500  lifetime use of cannabis  positive and negative psychotic symptoms  4.3 (95% CI: 1.0–17.9)  other drug use, depressive symptoms, sex, school grade  Henquet, Krabbendam, Spauwen, Kaplan, Lieb, Witchen, & van Os 2005  population based (14–24 years)  2,437  lifetime use of cannabis at baseline  psychotic symptoms  1.7 (95% CI: 1.1–2.5)  age, sex, socioeconomic status, urbanicity, trauma, predisposition for psychosis, other drug use, tobacco use, alcohol use  Mechanism of action for CBD: Cannabidiol >> inhibit degradation of anandamide >> maintain level of anandamide. Anandamide >> degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. In the results of this study2 >> they observed a significant correlation in patients on Cannabidiol treatment between clinical improvement and serum anandamide levels. The correlation suggests that the ability of CBD to inhibit FAAH enzyme activity >> stimulating intrinsic anandamide signaling might be relevant to antipsychotic properties. The study states that serum endocannabinoids less useful in early stages BUT more valuable in more chronic cases. They supported their interpretation by: First, in a relatively large cohort of antipsychotic-naïve schizophrenic patients (n=47), cerebrospinal anandamide levels were found to be inversely correlated with psychotic symptoms. Second, high-risk subjects for psychosis who exhibited lower cerebrospinal levels of anandamide also showed a higher risk for transiting to frank psychosis. Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.10 CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as ‘skunk’ (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.10 references: 1. Medicinal Cannabinoid FAQ: What are THC, CBD, CBN C and …? | PAB. Medicinal Cannabinoid FAQ: What are THC, CBD, CBN, CBC and …? | Pure Analytics Blog. http://pureanalytics.net/blog/2011/12/12/medicinal-cannabinoid-faq-what-are-thc-cbd-cbn-cbc-and-…/. Accessed June 5, 2018. 2. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2(3):e94-e94. doi:10.1038/tp-. HALL W, DEGENHARDT L. Cannabis use and the risk of developing a psychotic disorder. World Psychiatry. 2008;7(2):68-71. doi:10.1002/j-.tb00158.x 4. Macleod J. Cannabis use and psychosis: the origins and implications of an association. Adv Psychiatr Treat. 2007;13(6):-. McGrath J, Welham J, Scott J, et al. Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults. Arch Gen Psychiatry. 2010;67(5):440. doi:10.1001/archgenpsychiatry.2010.6 6. Georgopoulos G, Stowkowy J, Liu L, et al. The role of a family history of psychosis for youth at clinical high risk of psychosis. Early Interv Psychiatry. August 2017. doi:10.1111/eip.12471 7. Verdoux H, Gindre C, Sorbara F, Tournier M, Swendsen JD. Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychol Med. 2003;33(1):23-32. http://www.ncbi.nlm.nih.gov/pubmed/-. Accessed June 8, 2018. 8. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res. 2015;162(1-3):153-161. doi:10.1016/j.schres-. Henquet C, Murray R, Linszen D, van Os J. The environment and schizophrenia: the role of cannabis use. Schizophr Bull. 2005;31(3):-. Morgan CJA, Gardener C, Schafer G, et al. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol Med. 2012;42(2):391-400.