A Brief Background on Cannabis: From Plant to Medical Indications

Cannabis has been used as a medicinal plant for thousands of years. As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes.

  • Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors. Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptor types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System.
  • The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol. The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the “cytochrome P450 system to 11-hydroxy-THC”, which is also psychoactive.

Cannabis and cannabinoids have been indicated for several medical conditions. There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but there is not good evidence to support its efficacy. Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.

Medical Indications for Cannabis Use

Nausea & Vomiting

Researchers have found that when a sublingual mixture containing equal parts of THC and CBD was added to the standard antiemetic (anti-vomiting) therapy, it improved the nausea in patients undergoing chemotherapy.

  • One study used a commercial product undergoing U.S. Food and Drug Administration (FDA) approval, Nabiximols (Sativex), a sublingual spray that contains THC:CBD in a 1:1 ratio. In that study, researchers showed that 71.4% of patients in the treatment group had a complete resolution in their nausea and vomiting.
  • In another study that used National Institute of Drug Abuse–sourced cannabis (900 mg cannabis cigarettes containing 1.93% THC), it was shown that 14 of 15 patients had a reduction in nausea and vomiting in the THC group when compared with the placebo. They also showed a relationship between the blood concentration of THC and effectiveness; the higher the concentration of THC in the blood, the lower the incidence of nausea and vomiting.

Pain Associated with Multiple Sclerosis (MS)

Researchers found that cannabis-based medicines are probably effective for treating the neuropathic pain and painful spasms associated with MS.

  • It has also been shown that cannabis-based medicines reduced the patient-reported spasticity associated with MS

Neuropathic Pain

Cannabis has been found to treat neuropathic pain associated with diabetes, human immunodeficiency virus (HIV), and other causes.

  • Researchers found a dose-dependent reduction in pain intensity in response to inhaled cannabis in patients with diabetic peripheral neuropathy.
  • HIV-positive patients found relief from pain by smoking one cigarette of cannabis flower containing 3.56% THC three times per day. Most other studies on neuropathic pain related to other causes have been performed with Nabiximols (Sativex) containing THC:CBD in equal ratios and generally show positive results.

Chronic Pain Related to Cancer

Cannabis can be used to treat chronic pain associated with cancer and other causes. Studies generally suggested improvements in chronic pain measures associated with taking cannabis in cancer patients.

  • Most studies have been performed with Nabiximols (Sativex) containing THC:CBD in a 1:1 ratio and generally show positive results.

Insomnia

Insomnia is a multifaceted disorder. Some patients experience insomnia because they have another condition that makes it difficult to sleep. Cannabis products such as Nabiximols (Sativex) were associated with a greater average improvement in sleep by targeting indirect effects.

  • They summarized that in studies in 2000 subjects with 1000 patient years of exposure, it demonstrated marked improvement in patient-reported sleep parameters in patients with a wide variety of pain conditions.
  • In a safety follow-up study, about 40% of subjects attained good-to-very-good sleep quality with maintenance of up to 2 years, indicating no or limited tolerance.

Anxiety

  • Researchers showed that patients with social anxiety disorder treated with oral capsules of 600 mg CBD had lower anxiety measured by a reduction of 16.5 on a 100-point scale in a simulated public speaking test.
  • Other studies looked at the effect of oral CBD (400 or 600 mg) on anxiety using brain imaging studies and subjective measures of anxiety symptoms; compared with a placebo, CBD decreased subjective anxiety in subjects given THC.

Loss of Appetite

  • In one study, oral THC increased daily caloric intake, weight gain, and the number of times the patients ate per day. It was found that the higher the dosage, the larger the weight gain. The individuals in the group that was treated with the highest dosage (four times a day of 10 mg THC, as dronabinol) had a 2.2 lb (1 kg) increase in weight after 4 days of treatment.

Post-Traumatic Stress Disorder (PTSD)

Cannabis can be used to treat PTSD symptoms including insomnia and nightmares.

  • In an open-label pilot study, 34 patients experienced total cessation or lessening of severity of nightmares (28 patients had total cessation of nightmares and 6 had satisfactory reduction). In a follow-up double-blind treatment study, they showed that after starting Nabilone (an oral synthetic THC) treatment, 7 out of 10 subjects scored nightmare reduction as very much improved or much improved.
  • Subjects have shown an increase in the number of hours slept (mean 5.0 h pre-treatment versus 7.2 h post-treatment) as well as fewer nightmares (mean 5.2 pre-treatment versus 0.9 post-treatment).
  • Other studies have shown significant improvement in sleep quality and reduced frequency of nightmares. In addition, patient self-reported tools showed improvement in reducing nightmare frequency.

Tourette’s Syndrome

  • Case reports (reports written about individuals instead of being randomized, blinded studies) have suggested that smoking cannabis can reduce tics and that the therapeutic effects of cannabis might be due to anxiety-reducing properties of cannabis rather than to a specific anti-tic effect.
  • Patients also reported improvement in comorbid symptoms with cannabis including obsessive-compulsive symptoms, attention, impulsivity, anxiety, irritability, rage outbursts, and sleep.

Epilepsy

Various studies have demonstrated the effectiveness of CBD, and on June 25, 2018, the FDA approved EPIDIOLEX®, an oral solution of cannabidiol, for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older.

  • Examples of studies showing effectiveness in epileptic seizures include a study that demonstrated CBD to reduce seizure frequency in children and young adults with highly treatment-resistant epilepsy.
  • Another study reported that the median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with CBD, in patients with Dravet syndrome in the age range of 2.3–18.4 years old.
  • In one older review of four studies looking at children with treatment-resistant epilepsy, half the studies showed a reduction in seizure frequency.

Conclusion

This relatively new field of research, limited by prohibitive regulations because of political reasons, needs more intense study. Cannabis has a long history of being used medicinally. From its start as an industrial fiber plant, cannabis is increasingly being recognized for its medical properties.

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