The International Nonproprietary Name Dronabinol, also known as delta-9-tetrahydrocannabinol, or under the trade names Marinol, Syndros, Reduvo and Adversa, is a generic name for the molecule of delta-9-tetrahydrocannabinol in the pharmaceutical context. It has indications as an appetite stimulant,

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They m ...

, and sleep apnea reliever and is approved by the FDA as safe and effective for

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

-induced anorexia and

chemotherapy-induced nausea and vomiting Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. ...

only. Dronabinol is the principal

psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

constituent

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

form, (−)-''trans''-Δ⁹-

tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...

, found in

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: '' Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternative ...

. Dronabinol does not include any other

(THC)

isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...

or any

cannabidiol Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD in ...

Medical uses

Appetite stimulant and anti-emetic

Dronabinol is used to stimulate appetite and therefore weight gain in patients with HIV/AIDS and cancer. It is also used to treat chemotherapy-induced nausea and vomiting.

Analgesic

Dronabinol demonstrated analgesic efficacy in a majority of studies in chronic pain, the data in acute pain is less conclusive.

Cannabis addiction

Dronabinol may be useful in treating cannabis addiction as it has been shown to reduce cannabis withdrawal symptoms and the subjective effects of marijuana.

Sleep apnea

Dronabinol demonstrates significant improvement in sleep apnea scores. Phase 2B clinical trials were completed in 2017 for FDA approval for this indication.

Overdose

A mild overdose of dronabinol presents drowsiness, dry-mouth,

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and d ...

, and

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

; whereas a severe overdose presents

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

, slurred speech, decreased motor coordination, and

postural hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

History

While dronabinol was initially approved by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

on May 31, 1985, it was not until May 13, 1986, the

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic en ...

(DEA) issued a Final Rule and Statement of Policy authorizing the "rescheduling of synthetic dronabinol in

sesame oil Sesame oil is an edible vegetable oil derived from sesame seeds. The oil is one of the earliest-known crop-based oils. Worldwide mass modern production is limited due to the inefficient manual harvesting process required to extract the oil. ...

and encapsulated in soft

gelatin Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...

capsules from Schedule I to Schedule II" (DEA 51 FR 17476-78). This permitted medical use of Marinol, albeit with the severe restrictions associated with Schedule II status. For instance, refills of Marinol prescriptions were not permitted. On April 29, 1991, the Commission on Narcotic Drugs, in accordance with article 2, paragraphs 5 and 6, of the Convention on Psychotropic Substances of 1971, decided that Δ⁹-tetrahydrocannabinol (also referred to as Δ⁹-THC) and its stereochemical variants should be transferred from Schedule I to Schedule II of that Convention. This released Δ⁹-THC from many of the restrictions imposed by the Convention, facilitating its marketing as medication. An article published in the April–June 1998 issue of the Journal of Psychoactive Drugs found that "Healthcare professionals have detected no indication of scrip-chasing or doctor-shopping among the patients for whom they have prescribed dronabinol". The authors state that Marinol has a low potential for abuse. In 1999, in the United States, Marinol was rescheduled from Schedule II to III of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...

, reflecting a finding that THC had a potential for abuse less than that of

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

and

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and bro ...

. This rescheduling constituted part of the argument for a 2002 petition for removal of cannabis from Schedule I of the Controlled Substances Act, in which petitioner

Jon Gettman Jon B. Gettman (born August 20, 1957) is a marijuana rights activist, a leader of the Coalition for Rescheduling Cannabis, and a former head of the National Organization for the Reform of Marijuana Laws. He has a PhD in public policy and regiona ...

noted, "Cannabis is a natural source of dronabinol (THC), the ingredient of Marinol, a Schedule III drug. There are no grounds to schedule cannabis in a more restrictive schedule than Marinol". In 2003, the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

Expert Committee on Drug Dependence recommended transferring THC to Schedule IV of the Convention, citing its medical uses and low abuse potential. In 2019, the Committee recommended transferring Δ⁹-THC to Schedule I of the Single Convention on Narcotic Drugs of 1961, but its recommendations were rejected by the

United Nations Commission on Narcotic Drugs The Commission on Narcotic Drugs (CND) is one of the functional commissions of the United Nations' Economic and Social Council (ECOSOC), and is the central drug policy-making body within the United Nations System. The CND also has important man ...

Society and culture

Brand names

Dronabinol is marketed as Marinol and Syndros, a registered trademark of Solvay Pharmaceuticals. Dronabinol is also marketed, sold, and distributed by PAR Pharmaceutical Companies under the terms of a license and distribution agreement with SVC pharma LP, an affiliate of Rhodes Technologies for Marinol and Insys Pharmaceuticals for Syndros. Dronabinol is available as a prescription drug (under Marinol and Syndros ) in several countries including the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwee ...

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring coun ...

and

Australia Australia, officially the Commonwealth of Australia, is a sovereign country comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands. With an area of , Australia is the largest country by ...

. In

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by to ...

, Tetra Bio-Pharma filed a New Drug Submission (NDS) with Health Canada for its Dronabinol Soft Gel capsules to be marketed as REDUVO™. Tetra has two other dronabinol drugs with new routes of administration which limit first-pass metabolism; an inhaled THC-based dronabinol drug and their mucoadhesive-delivery dronabinol drug Adversa®, which are both in the accelerated 505(b)(2) New Drug Application (NDA) pathway for the U.S. and Canadian markets.

In the United States, Marinol is a Schedule III drug, available by prescription, considered to be non-

narcotic The term narcotic (, from ancient Greek ναρκῶ ''narkō'', "to make numb") originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates ...

and to have a low risk of physical or mental dependence. Efforts to get cannabis rescheduled as analogous to Marinol have not succeeded thus far, though a 2002 petition has been accepted by the DEA. As a result of the rescheduling of Marinol from Schedule II to Schedule III, refills are now permitted for this substance. Marinol's U.S. Food and Drug Administration (FDA) approval for medical use has raised much controversy as to why cannabis is still illegal at the federal level.

Comparisons with medical cannabis

Female cannabis plants not only contain dronabinol but at least 113 other cannabinoids, including

(CBD), thought to be the major

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

that helps people with

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...

; and

cannabichromene Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, is an anti-inflammatory which may contribute to the pain-killing effect of cannabis. It is one of the hundreds of cannabinoids found i ...

(CBC), an

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

which may contribute to the pain-killing effect of cannabis. It takes over one hour for Marinol to reach full systemic effect, compared to seconds or minutes for

smoked Smoking is the process of flavoring, browning, cooking, or preserving food by exposing it to smoke from burning or smoldering material, most often wood. Meat, fish, and '' lapsang souchong'' tea are often smoked. In Europe, alder is the tra ...

or vaporized cannabis. Mark Kleiman, director of the Drug Policy Analysis Program at UCLA's School of Public Affairs said of Marinol, "It wasn't any fun and made the user feel bad, so it could be approved without any fear that it would penetrate the recreational market, and then used as a club with which to beat back the advocates of whole cannabis as a medicine." Clinical trials comparing the use of cannabis extracts with Marinol in the treatment of cancer

cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart fa ...

have demonstrated equal efficacy and well-being among subjects in the two treatment arms. United States federal law currently registers dronabinol as a Schedule III controlled substance, but all other cannabinoids remain Schedule I, except synthetics like nabilone and HU-308.

References

{{reflist

External links

Medlineplus.gov on Dronabinol
Acetylcholinesterase inhibitors Amorphous solids Antiemetics AbbVie brands Appetite stimulants Aromatase inhibitors Benzochromenes Entheogens Euphoriants Tetrahydrocannabinol Social problems in medicine