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What is medical cannabis?

First of all, what is cannabis? According to the website of the Ministry of Health, Labor and Welfare, “cannabis is cannabis grass (Cannabis sativa el) and its products” is defined. And in Japan, from the viewpoint of drug abuse prevention, the Cannabis Control Law enacted in 1948 regulates the manufacture of drugs containing cannabis raw materials (excluding dried stems and seeds), and also regulates research such as clinical trials. I am. As you can see from the website of the Ministry of Health, Labor and Welfare that I referred to, cannabis plants have taken root in the image of “illegal drugs”.

However, in recent years, the idea of ​​Medical cannabis or Medical marijuana has become mainstream, and various countries in the West have allowed the use of medical cannabis. In addition, medical cannabis is now available in Asian countries such as South Korea and Thailand. In Japan, cannabis used for such medical purposes is generally called “medical cannabis”. It seems that the image of “drug” has not been wiped out yet.

But importantly, even in Western countries where cannabis can be used for medical purposes, cannabis plants themselves and crude extracts are not approved as pharmaceuticals. Each of the cannabinoids, a chemical substance extracted from cannabis, is approved as a drug, and drugs containing this ingredient are basically used under the supervision of healthcare professionals. increase.

What is the current state of medical cannabis in Japan?

As mentioned above, in Japan, cannabis plants are strictly regulated not only as a luxury item, but also for medical use and research for that purpose. In the view of the Ministry of Health, Labor and Welfare, synthetic cannabinoids that resemble cannabis-derived cannabinoids are treated as narcotics and psychotropic drugs under the Psychotropics Control Law, so research is possible. Regarding cannabis-derived cannabinoids, the following remarks were recorded in the minutes of the Diet at the “198th House of Councilors Special Committee on Okinawa and Northern Issues” held on March 19, 2019 (overseas). About Epidiolex, a cannabis-derived refractory epilepsy drug approved by the House of Councilors).

“137 Kazuhiko Mori

(Omitted). .. .. Article 4, Paragraph 1 of the Cannabis Control Law of Japan stipulates that no one shall apply, deliver, or receive an application of a drug manufactured from cannabis. In addition, there is a provision that cannabis must not be imported unless a person who has obtained a license to use it for the purpose of researching cannabis from the prefectural governor, that is, a cannabis researcher has obtained the permission of the Minister of Health, Labor and Welfare. .. Therefore, under the current law, if the drug you pointed out is manufactured from cannabis, the drug cannot be applied to patients in Japan and cannot be imported for the purpose of application. It is. “

“138 Kozo Akino

In that case, if it is not good as a drug, how about using it as a clinical trial? “

“139 Kazuhiko Mori

(Omitted). .. .. Under the guidance of a doctor who is a cannabis researcher, it is possible to use Epidiolex imported with the permission of the Minister of Health, Labor and Welfare for patients in Japan as a drug to be studied.

 In addition, it is necessary that this clinical trial is conducted only for the target patients specified in the plan based on an appropriate implementation plan, and when the implementation plan is delivered, that I think that it is necessary to confirm the contents firmly. “

Thus, in the government’s view, it seems possible to use cannabis-derived drugs as clinical trials. Also, on September 5, 2019, it seems that the patient group has submitted a request for Epidiolex approval to the Minister of Health, Labor and Welfare so that it will be approved not only as a clinical trial but also as a drug.

What is the difference between THC and CBD?

There are many cannabinoids extracted from cannabis, but they are mainly used as pharmaceuticals mainly for the components tetrahydrocannabinol (THC) and cannabidiol (CBD). These two components have different structures, and their actions in the body also change. In particular, cannabidiol (CBD), unlike tetrahydrocannabinol (THC), is said to have no euphoric or psychological side effects (so-called high mood-like effects) associated with the word cannabis. increase.

More specifically, cannabinoids such as CBD and THC are said to act on cannabinoid receptors such as CB1 and CB2. CB1 receptors are abundant mainly in the central nervous system, CB2 receptors are abundant in peripheral tissues, and THC has affinity for both CB1 and CB2 receptors. And CBD has a more selective affinity for the CB2 receptor. It can be said that this difference is manifested as the presence or absence of side effects (to the psyche) to the central nervous system.

In addition, cannabis strains with high THC content and low CBD content are said to have more psychological side effects than strains with similar amounts of both components, and an interesting paper was published that took notice of this. rice field. A study at the University of Western Ontario in October 2019 suggests that CBD may suppress the activation of extracellular signal-regulated kinase (ERK), which causes THC to have psychiatric effects.

In this way, even if the ingredients are extracted from the same cannabis, the way they work will change significantly.

Benefits of using with ingredients of medical cannabis 

The components of medical cannabis used around the world can be broadly divided into synthetic cannabinoids and cannabis-derived cannabinoids. For example, the former contains nabilone and dronabinol, and the latter contains nabiximols (a combination of THC and CBD) and cannabidiol (CBD). Looking at the indications for drugs containing these ingredients,

  • Nabilone: ​​Suppression of nausea and vomiting when using anticancer drugs (when conventional antiemetics are ineffective)
  • Dronabinol: Loss of appetite and weight loss in AIDS patients. Suppression of nausea and vomiting when using anticancer drugs (when conventional antiemetics are ineffective)
  • Nabiximols: Spasticity in multiple sclerosis (when conventional antispasmodics are ineffective)
  • Cannabidiol: suppression of epileptic seizures in refractory epilepsy in children (Lennox-Gastaut syndrome and Dravet syndrome)

Thus, even if medical cannabis is not the first choice for treatment, it is one of the benefits for those suffering from the above symptoms and illnesses to have more treatment options.

What kind of illness is said to be effective?

As shown above, the cannabis component (including synthetic cannabinoids) is effective as an antiemetic, antispasmodic, and antiepileptic drug, and is approved as a medical drug.

For example, looking at the results of research on cannabidiol, the meta-analysis “Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis” by Lattanzi, Simona et al. (2018) shows Lennox-Gastaut syndrome and Dravet syndrome. Four studies are being investigated, including 550 patients with intractable epilepsy. The study focuses on the rate of decrease in monthly seizure frequency, resulting in at least 50% of patients in the cannabidiol 20 mg group and 21.2% in the placebo (placebo) group. Reduced seizures have been reported (risk ratio 1.76, 95% CI 1.07-2.88; p = 0.025). Generally, if the p-value is 0.05 or less, the result is statistically significant, so it can be said that administration of cannabidiol is effective in suppressing seizures. Side effects appear to occur in 87.9% of the cannabidiol-treated group and 72.2% of the placebo group (risk ratio 1.22, 95% CI 1.11-1.33; p <0.001). In addition, there was a discontinuation of administration due to side effects with a probability of about 5 times (risk ratio 5.59, 95% CI 1.87–16.73; p = 0.002). However, the side effects that have occurred do not seem to be worse than existing treatments such as drowsiness, loss of appetite, and diarrhea.

In addition, cannabinoids have been suggested to be effective against Parkinson’s disease and the motor function symptoms that occur during its treatment. In the paper “Evidence for the use of cannabinoids in Parkinson’s disease” published by Carsten Buhmann et al. In May 2019, various literatures on cannabinoids and Parkinson’s disease are investigated. This paper suggests that in Parkinson’s disease, high levels of cannabinoid receptors are found in the basal ganglia, and that cannabinoids regulate the excessive action of dopamine in the brain to improve “levodopa-induced dyskinesia.” I am paying attention to. In fact, a 2001 study seems to report that nabilone reduced “levodopa-induced dyskinesia.”

On the other hand, however, Buhmann et al. Show statistically significant differences, pointing out that clinical studies such as random-blind trials with a high level of evidence have rarely been conducted. For people undergoing treatment for Parkinson’s disease, movement disorders are a major quality of life issue. I hope that research will progress in the future and that its efficacy and safety will be recognized.

Furthermore, various papers suggest that cannabinoids are also effective for insomnia and schizophrenia caused by ADHD and PTSD. There are some papers that do not show statistically significant differences and that are likely to have many biases, but it can be said that research on medical cannabis (cannabinoids) is definitely progressing day by day.

 

References

Ministry of Health, Labor and Welfare “Cannabis is dangerous now!”

Diet Minutes Search System “198th House of Councilors Special Committee on Okinawa and Northern Issues No. 3 March 19, 2019”

Japan Epilepsy Association “Epidiolex ® CBD: Request for Cannabidiol Drug Approval”

National Institute on Drug Abuse “Marijuana as Medicine”

European Monitoring Center for Drugs and Drug Addiction “Medical use of cannabis and cannabinoids”

EMC “Sativex Oromucosal Spray”

Simona Lattanzi, Francesco Brigo, Eugen Trinka, Gaetano Zaccara, Claudia Cagnetti, Cinzia Del Giovane et al. “Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis”

Beedham W, Sbai M, Allison I, Coary R, ​​Shipway D. “Cannabinoids in the Older Person: A Literature Review.”

Carsten Buhmann, Tina Mainka, Georg Ebersbach, Florin Gandor. “Evidence for the use of cannabinoids in Parkinson’s disease”

FDA “EPIDIOLEX (cannabidiol) oral solution”

FDA “CESAMET ™ (nabilone) Capsules – FDA”

FDA “MARINOL (dronabinol) capsules, for oral use”

Roger Hudson, Justine Renard, Christopher Norris, Walter J. Rushlow, Steven R. “Laviolette. Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus Through Bi-Directional Control of ERK1-2 Phosphorylation.”

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