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''-Δ
9-
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
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' ...
(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 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 ...
(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.
See also
* Cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
** 11-Hydroxy-THC
11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC, alternatively numbered as 7-OH-Δ1-THC), usually referred to as 11-hydroxy-THC, is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after THC is consumed.
...
, metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
of THC
** Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid r ...
, 2-Arachidonoylglycerol, endogenous cannabinoid agonists
** 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' ...
** 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 ...
(CBD)
** Cannabinol
Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).
CBN w ...
(CBN), a metabolite of THC
** Dimethylheptylpyran
Dimethylheptylpyran (DMHP, 3-(1,2-dimethylheptyl)-Δ6a(10a)-THC, 1,2-dimethylheptyl-Δ3-THC, A-40824, or EA-2233) is a synthetic analog of THC, which was invented in 1949 during attempts to elucidate the structure of Δ9-THC, one of the act ...
** Parahexyl
** Tetrahydrocannabinolic acid, the biosynthetic precursor for THC
** HU-210, WIN 55,212-2, JWH-133, synthetic cannabinoid agonists ( neocannabinoids)
* Medical cannabis
Medical cannabis, or medical marijuana (MMJ), is cannabis and cannabinoids that are prescribed by physicians for their patients. The use of cannabis as medicine has not been rigorously tested due to production and governmental restriction ...
(pharmaceutical cannabinoids)
** Epidiolex
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 incl ...
(prescription form of purified cannabidiol derived from hemp used for treating some rare neurological diseases)
** Sativex
** Nabilone, a novel synthetic cannabinoid analog ( neocannabinoid)
** HU-308, a highly potent synthetic cannabinoid CB2 agonist
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