Unconventional Neuropharmacology:Cannabis and Lysergic acid dithylamide

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Laboratory of Neuro Imaging at UCLA and Martinos Center for Biomedical Imaging at MGH [4]

Psychiatric and physical health is of huge societal concern. This concern should include the best treatment options for the patients that highlight drug treatments of diseases with effective, non-addictive and low side effect causing drugs. Current substances such as oxycontin have become a major street drug problems in many places due to their highly addictive nature whereas other less addictive drugs may be overlooked due to their legality not their effectiveness[1]. With rising numbers of individuals being diagnosed with mental disorders and low treatment affectivity options, it is important to examine other drugs which may increase onset of effect and help patients suffering better their quality of life. Current neuropharmacological options may already exist such as cannabis[3]. This drug has been shown to be a very promising for many illnesses including chronic pain; excitingly it is not addictive and has minimal side effects. Furthermore, Lysergic acid dithylamide (LSD) has also been shown to help with many mental illnesses such as alcoholism [2] . These two drugs have many more potential target treatment options and meta-analyses from the beginning of research into these drugs are readily available and show promising numbers.

Cannabis

History and Current Societal Influence

THC Molecule
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Courtesy of TruthonPot

Cannabis, otherwise known as marijuana or weed, is a naturally occurring plant that originated in Asia. Yanghai tombs in central China showed evidence of cannabis use in from 2,500-2800 year old burial sites of a shaman [5]. This is very possibly not the oldest use of cannabis as much ancient rituals appear to involve the use of cannabis. Even though the drug had been used by individuals for more than simply recreational use for thousands of years, at the beginning of the 20th century many countries began criminalizing its use [10]. The active compound in cannabis was found to be Tetrahydrocannbinal (THC), which acts on cannabinoid receptors in the brain[2]. Certain areas of the world are beginning to allow medicinal marijuana use for certain diseases and as recently highly publicized, the state of Colorado has just legalized it

Potential treatments uses of Cannabis: Human Trial Meta-Analyses/ Phase III trial for Cannabis

Use in chemotherapy patients

Patients undergoing chemotherapy often face extreme side effects that drastically reduce quality of life. This makes it necessary to look at options to help patients undergoing chemotherapy in order to help the healing process of both the cancer and chemotherapy effects. A meta-analysis study showed that cannabis could be significantly beneficially in treating the decreased appetite and nausea caused by chemotherapy [9]. This meta-analysis used 30 trials, and looked at patient use, satisfaction and efficacy of three drugs; dronabinol a THC derivative, a placebo control and non-cannabis derived antiemetics. It was found that not only was dronabinol most preferred by patients but that it also was seen as statistically significant in decreasing nausea and vomiting compared to other drugs [9].

Treatment for Anorexia

THC is able to directly target the hypothalamus and this interaction is what current researchers believe causes the increased appetite when individuals use cannabis[12]. Current trials were conducted to see whether cannabis could be used to treat Cancer-Related Anorexia-Cachexia Syndrome. The focus of this trial was to see whether a Cannabis Extract, a synthesized drug, or delta-9-THC, the natural form, showed any differences in patient outcomes. Patient outcomes predominately focussed on appetite changes and weight fluctuations. The study found no significant difference between the extract and the natural form, but did see increased appetite and weight compared to the placebo group. This suggests promising potential treatments for not only another form of cancer, but potentially in the future, treatment for another big problem facing many people; anorexia.

Alleviation of chronic pain

Generalized chronic pain is a serious and difficult to treat ailment that many people face in their daily lives. Many current treatment options include the use of highly addictive drugs such as oxycontin which can lead to even more complications than the symptom it attempts to treat [4]. Luckily, Martin-Sanchez et al. attempted to debunk negative views on cannabis as a treatment option for individuals with chronic pain. Statistical analysis of 18 trials showed favour towards marijuana use for pain, however, it was not entirely conclusive [7]. More conlusively however, meta analysis of pain treatment for Multiple Sclerosis by cannabis was done that showed significant results for each type of cannabinoid and when all derivatives were compiled showed p<0.001 [6]. The difference between these studies highlights the difficulties in studying generalized pain, and how important it is to find treatments that work for specific types of pain.

Lysergic acid dithylamide (LSD)

History and Origin

LSD Molecule
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From DrugProfiles[14]

Lysergic acid dithylamide (LSD) was developed by Dr Hofmann in 1938 and quickly became widely used in psychiatric therapies and for human trial studies. The development of this drug helped form the developing understanding of the serotonin system in humans and for further research into drugs that act of the 5-HT receptor [11]. Use for psychotherapy and research was soon halted; in the late 1960’s it was deemed illegal in the US and even though experiments continued in Switzerland (the country of origin), the criminality of the drug made it nearly impossible to study.

Treatment for diseases by LSD based off Human Trials

Psychotherapy under LSD use

Thousands upon thousands of patients were treated psychiatrically with the use of LSD from the 1940’s-60’s [1]. Chandler said that the use of LSD could help individuals cope and expose inner traumas and subconscious fears to enable more productive psychotherapy sessions (1960). Currently, research suggests that LSD is still beneficial but that it is important that it is done in a controlled and safely monitored environment due to potential side effects [3].

Alcohol Addiction Treatment

Amazingly, it has been shown that one dose, administered in a controlled setting, is able to significantly decrease an alcohol abuser’s alcohol use [7]. The meta-analysis was conducted using 536 cases within 6 trials which showed significant benefits to alcohol addiction recovery and relapse. The use of LSD for alcoholism treatment is well documented in literature with the most papers released in the 60’s when research on this drug was booming.

Alleviation of anxiety; End of life therapeutic benefits

Perhaps one of the most difficult issues all humans face is death. The fear of death when diagnosed with a terminal illness can be extremely overwhelming and create huge anxieties [3]. As LSD has been used before for treatment of general mood disorders and anxieties during the 1960’s, it made a mere perfect candidate drug for use in a very recent experiment published in 2014 that attempts to help terminally ill patients find comfort. Gasser et al conducted a 12 person trial where 8 were given high doses compared to 4 on low doses. Patients given the high dose saw extremely positive results at every new session, the 4 patients on the low dose were switched to the high dose to allow them to benefit from the positive effects. The trial saw 20% reduction in anxiety after each LSD-assisted therapy session which persisted more than a year [3].

Bibliography
1. Chandler et al (1960). “Lysergic Acid Diethylamide (lsd-25) as a Facilitating Agent in Psychotherapy.” A.M.A. Archives of General Psychiatry 2, no. 3: 286–299.
2. Gaoni, Y Mechoulam, R. (1964). "Isolation, structure and partial synthesis of an active constituent of hashish". Journal of the American Chemical Society 86 (8): 1646–1647
3. Gasser, Peter, Dominique Holstein, Yvonne Michel, Rick Doblin, Berra Yazar-Klosinski, Torsten Passie, and Rudolf Brenneisen. (2014). “Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-Threatening Diseases.” The Journal of Nervous and Mental Disease.
4. Hays, Lon R. (2004) “A Profile of OxyContin Addiction" Journal of Addictive Diseases 23, no. 4: 1–9.
5. Jiang Hong-En, et al. (2006). "A new insight into Cannabis sativa (Cannabaceae) utilization from 2500-year-old Yanghai tombs, Xinjiang, China". Journal of Ethnopharmacology 108 (3): 414–22.
6. Iskedjian, Michael, Basil Bereza, Allan Gordon, Charles Piwko, and Thomas R. Einarson. (2006). “Meta-Analysis of Cannabis Based Treatments for Neuropathic and Multiple Sclerosis-Related Pain.” Review-article.
7. Krebs, Teri S., and Pål Ørjan Johansen. (2012) “Lysergic Acid Diethylamide (LSD) for Alcoholism: Meta-Analysis of Randomized Controlled Trials.” Journal of Psychopharmacology
8. Martín-Sánchez, Eva, Toshiaki A. Furukawa, Julian Taylor, and Jose Luis R. Martin. (2009). “Systematic Review and Meta-Analysis of Cannabis Treatment for Chronic Pain.” Pain Medicine 10, no. 8: 1353–1368
9. Machado Rocha, F C, S C Stéfano, R De Cássia Haiek, L M Q Rosa Oliveira, and D X Da Silveira.(2008) “Therapeutic Use of Cannabis Sativa on Chemotherapy-Induced Nausea and Vomiting among Cancer Patients: Systematic Review and Meta-Analysis.” European Journal of Cancer Care 17, no. 5: 431–443.
10. Levinson, David (2002). Encyclopedia of Crime and Punishment. SAGE Publications. p. 572
11. Schindler, Emmanuelle A. D., Kuldip D. Dave, Elaine M. Smolock, Vincent J. Aloyo, and John A. Harvey. (2012) “Serotonergic and Dopaminergic Distinctions in the Behavioral Pharmacology of 1-(2,5)-Dimethoxy-4-Iodophenyl)-2-Aminopropane (DOI) and Lysergic Acid Diethylamide (LSD).” Pharmacology, Biochemistry, and Behavior 101, no.1: 69–76.
12. Strasser, F. Luftner, D. Possinger, Kurt. Ernst, Germot. Ruhstaller, T. Meissner,W. et al. (2006).
“Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients with Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial from the Cannabis-In-Cachexia-Study-Group.” Journal of Clinical Oncology 24, no. 21: 3394–3400.
13. Vollenweirder, F. X. & Kometer, M. (2010). “The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders.” Nature Neurosci. 11, 642-651

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