Antiemetic properties of medical cannabis

Medical cannabis has been increasingly recognized as a potential treatment option for chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy treatment. Chemotherapy is a common cancer treatment that works by targeting rapidly dividing cells, including cancer cells. However, chemotherapy drugs also affect healthy cells in the body, including the cells lining the gastrointestinal tract, which can lead to nausea and vomiting. Antiemetic medications are often used to manage CINV, but they can be ineffective in some patients and have significant side effects.

Cannabis plants contain a number of active compounds, known as cannabinoids, which have been found to have antiemetic properties. The two most well-known cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known for its psychoactive effects, while CBD is non-psychoactive and has been found to have a range of potential therapeutic benefits, including as an antiemetic.

Mechanism of Action

The exact mechanism by which cannabis exerts its antiemetic effects is not fully understood, but several potential mechanisms have been proposed. One proposed mechanism is through the modulation of the endocannabinoid system, which is a complex signaling system in the body that plays a role in a range of physiological processes, including pain sensation, mood, and appetite. The endocannabinoid system is comprised of two main receptors, CB1 and CB2, which are activated by endocannabinoids, which are naturally occurring compounds in the body, as well as by phytocannabinoids, which are compounds found in the cannabis plant. THC has been found to interact with CB1 receptors in the brain, which can lead to a reduction in nausea and vomiting.

Another proposed mechanism is through the modulation of the serotonin system in the brain. Serotonin is a neurotransmitter that plays a role in regulating mood, appetite, and nausea. THC has been found to stimulate the release of serotonin in the brain, which can lead to a reduction in nausea and vomiting.

Clinical Evidence

A number of clinical trials have investigated the potential of cannabis-based treatments for the management of CINV. These studies have found that cannabis-based treatments can be effective in reducing nausea and vomiting in patients undergoing chemotherapy, and can also improve appetite and quality of life.

One of the most well-known studies of cannabis-based treatments for CINV was a randomised, double-blind, placebo-controlled trial published in the New England Journal of Medicine in 1975. In this study, researchers found that THC was more effective than placebo in reducing nausea and vomiting in patients undergoing chemotherapy.

More recently, a number of studies have investigated the potential of CBD as an antiemetic. While CBD does not have the psychoactive effects of THC, it has been found to have a range of potential therapeutic benefits, including as an antiemetic. In a randomised, double-blind, placebo-controlled study published in the Annals of Oncology in 2010, researchers found that CBD was more effective than placebo in reducing nausea and vomiting in patients undergoing chemotherapy.

Side Effects

While cannabis-based treatments for CINV have been found to be generally well-tolerated, they can have side effects in some patients. The most commonly reported side effects of THC include dizziness, dry mouth, and changes in mood or perception. Additionally, THC can interact with some medications, including sedatives and benzodiazepines, which can lead to increased sedation and potential adverse effects. For this reason, it is important for patients to discuss the use of cannabis-based treatments with their healthcare provider. Additionally, patients should be aware of the potential psychoactive effects of THC and should avoid driving or operating heavy machinery while under the influence.

Research on Antiemetic properties of medical cannabis in literature

1. Cannaboinoid Antiemetic Therapy

Abstract 

There are currently three cannabinoids available on the pharmaceutical market. Dronabinol and nabilone are both synthetic tetrahydrocannabinol (THC) which the FDA has approved for the treatment of chemotherapy-induced nausea and vomiting (CINV) after the failure of a trial of first-line anti-emetics. Both are also FDA-approved to treat anorexia associated with AIDS. Recently, the FDA has also approved a cannabidiol (CBD) product to treat seizures associated with Lennox-Gastaut syndrome and Dravel syndrome in pediatric patients. However, there is no FDA-approved indication for its use as an anti-emetic. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cannabinoid antiemetics, pertinent for clinicians and other interprofessional team members to ensure the appropriate utilization of these drugs.

2. Cannaboinoid Antiemetic Therapy

Abstract

There are currently three cannabinoids available on the pharmaceutical market. Dronabinol and nabilone are both synthetic tetrahydrocannabinol (THC) which the FDA has approved for the treatment of chemotherapy-induced nausea and vomiting (CINV) after the failure of a trial of first-line anti-emetics. Both are also FDA-approved to treat anorexia associated with AIDS. Recently, the FDA has also approved a cannabidiol (CBD) product to treat seizures associated with Lennox-Gastaut syndrome and Dravel syndrome in pediatric patients. However, there is no FDA-approved indication for its use as an anti-emetic. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cannabinoid antiemetics, pertinent for clinicians and other interprofessional team members to ensure the appropriate utilization of these drugs.

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3. Cannabidiol in Humans—The Quest for Therapeutic Targets

Abstract

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.

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4. An efficient new cannabinoid antiemetic in pediatric oncology

Abstract

Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administerd (18 mg/m2 in edible oil, p.o.) to eight children, aged 3–13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.

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5. Chapter 72 - The Role of 5-HT1A Receptor, and Nausea and Vomiting Relief by Cannabidiol (CBD), Cannabidiolic Acid (CBDA), and Cannabigerol (CBG)

Abstract

Cancer patients undergoing chemotherapy often report nausea and vomiting as distressing symptoms associated with their treatment. Although vomiting is well managed with the advent of antiemetics, such as ondansetron and aprepitant, nausea is still not properly controlled. In order to screen potential antinausea compounds, a reliable animal model of nausea is necessary. We have utilized the rodent model of conditioned gaping as a preclinical tool to evaluate the antinausea properties of a number of compounds, including cannabinoids. In this chapter, the antinausea and antiemetic properties of cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabigerol (CBG) are presented. Additionally, the mechanisms of action for these cannabinoids are discussed in terms of activation of the 5-hydroxytryptamine1A (5-HT1A) receptors.

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6. Cannaboinoid Antiemetic Therapy

Abstract 

There are currently three cannabinoids available on the pharmaceutical market. Dronabinol and nabilone are both synthetic tetrahydrocannabinol (THC) which the FDA has approved for the treatment of chemotherapy-induced nausea and vomiting (CINV) after the failure of a trial of first-line anti-emetics. Both are also FDA-approved to treat anorexia associated with AIDS. Recently, the FDA has also approved a cannabidiol (CBD) product to treat seizures associated with Lennox-Gastaut syndrome and Dravel syndrome in pediatric patients. However, there is no FDA-approved indication for its use as an anti-emetic. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cannabinoid antiemetics, pertinent for clinicians and other interprofessional team members to ensure the appropriate utilization of these drugs.

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7.The Effectiveness of Common Cannabis Products for Treatment of Nausea

Abstract

Goals: 

We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time.

Background: 

Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products.

Study: 

Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea.

Results: 

By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of −3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min).

Conclusions: 

The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.

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8. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus

Abstract

BACKGROUND AND PURPOSE To evaluate the hypothesis that activation of somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis.

EXPERIMENTAL APPROACH The potential of systemic and intra-DRN administration of 5-HT1A receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT1A receptors and to modify the ability of the 5-HT1A agonist, 8-OH-DPAT, to stimulate [35S]GTPγS binding in rat brainstem membranes.

KEY RESULTS CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg−1, but not 40 mg·kg−1)-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose–response curve) at enhancing the ability of 8-OH-DPAT to stimulate [35S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping.

CONCLUSIONS AND IMPLICATIONS These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT1A autoreceptors in the DRN.

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