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| Trade names | Marinol, Syndros |
| Other names | (−)-trans-Δ9-tetrahydrocannabinol |
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| Dependence liability | Physical: Low Psychological: Low–moderate |
| Addiction liability | Relatively low[citation needed] |
| Routes of administration | By mouth |
| Drug class | Cannabinoid |
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| Pharmacokinetic data | |
| Bioavailability | POTooltip Oral administration: 6–20% |
| Onset of action | PO: 0.5–1 hour |
| Eliminationhalf-life | 25–36 hours |
| Duration of action | PO: 4–6 hours |
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| Chemical and physical data | |
| Formula | C21H30O2 |
| Molar mass | 314.469 g·mol−1 |
| 3D model (JSmol) | |
| Specific rotation | −152° (ethanol) |
| Boiling point | 155–157 °C (311–315 °F) 0.05mmHg,[1] 157–160°C @ 0.05mmHg[2] |
| Solubility in water | 0.0028 mg/mL (23 °C)[3] |
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Chemistry |
Pharmacology |
Law |
Dronabinol (INNTooltip International Nonproprietary Name), sold under the brand namesMarinol andSyndros, is thegeneric name for the molecule of (−)-trans-Δ9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as anappetite stimulant,antiemetic, andsleep apnea reliever[4] and is approved by the USFood and Drug Administration (FDA) as safe and effective forHIV/AIDS-inducedanorexia andchemotherapy-induced nausea and vomiting.[5][6][7]
Dronabinol is the principalpsychoactive constituentenantiomer form, (−)-trans-Δ9-tetrahydrocannabinol, found inCannabis sativa L. plants,[8] but can also be synthesized in laboratory. Dronabinol does not include any othertetrahydrocannabinol (THC)isomers or anycannabidiol (CBD).
Dronabinol is used tostimulate appetite and thereforeweight gain in patients withHIV/AIDS andcancer. It is also used to treatchemotherapy-induced nausea and vomiting.[9][10]
Dronabinol demonstratedanalgesic efficacy in a majority of studies inchronic pain, the data inacute pain is less conclusive.[11]
Dronabinol may be useful in treatingcannabis addiction as it has been shown to reducecannabis withdrawal symptoms and the subjective effects of cannabis.[12]
Dronabinol demonstrates significant improvement insleep apnea scores.[4][13][14][15] Phase 2B clinical trials were completed in 2017 for FDA approval for this indication.[16][17][18]
Common side effects of dronabinol includeeuphoria,drowsiness,dizziness,decreased motor coordination,anxiety,paranoia,confusion, and arapid heartbeat, among others.[19]
In a mildoverdose of dronabinol, the typical side effects are exacerbated, whereas a severe overdose presents withlethargy,slurred speech, severeataxia, andorthostatic hypotension.[5][20]
While dronabinol was initially approved by the United StatesFood and Drug Administration (FDA) on May 31, 1985,[21] it was not until May 13, 1986, theDrug Enforcement Administration (DEA), issued a Final Rule and Statement of Policy authorizing the "rescheduling of synthetic dronabinol insesame oil and encapsulated in softgelatin capsules fromSchedule I toSchedule II" (DEA 51 FR 17476-78). This permitted medical use of Marinol, albeit with the severe restrictions associated with Schedule II status.[22] For instance, refills of Marinol prescriptions were not permitted.
On April 29, 1991, theCommission on Narcotic Drugs, in accordance with article 2, paragraphs 5 and 6, of theConvention 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.[23]
An article published in the April–June 1998 issue of theJournal of Psychoactive Drugs found that "Healthcare professionals have detected no indication of script-chasing or doctor-shopping among the patients for whom they have prescribed dronabinol". The authors state that Marinol has a low potential for abuse.[24][better source needed]
In 1999, in the United States, Marinol was rescheduled from Schedule II toSchedule III of theControlled Substances Act, reflecting a finding that dronabinol had a potential for abuse less than that ofcocaine andheroin.[21] This rescheduling constituted part of the argument for a 2002 petition forremoval of cannabis from Schedule I of the Controlled Substances Act, in which petitionerJon Gettman 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".[25][better source needed]
In 2003, theWorld Health Organization Expert Committee on Drug Dependence recommended transferring THC to Schedule IV of the convention, citing its medical uses and low abuse potential.[26] In 2019, the Committee recommended transferring Δ9-THC to Schedule I of theSingle Convention on Narcotic Drugs of 1961, but its recommendations were rejected by theUnited Nations Commission on Narcotic Drugs.[27]
Dronabinol is marketed as Marinol and Syndros,[28] a registered trademark ofSolvay 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.[citation needed] Dronabinol is available as a prescription drug (under Marinol and Syndros[29]) in several countries including the United States, Germany, South Africa and Australia.[30] In Canada, Tetra Bio-Pharma filed a New Drug Submission (NDS) with Health Canada for its Dronabinol Soft Gel capsules to be marketed as REDUVO™.[31] 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.[32]
In the United States, Marinol is aSchedule III drug, available by prescription, considered to be non-narcotic 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 a2002 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[33] as to why cannabis is still illegal at the federal level.[34]
Female cannabis plants not only contain dronabinol but at least 113 other cannabinoids,[35] includingcannabidiol (CBD), thought to be the majoranticonvulsant that helps people withmultiple sclerosis;[36] andcannabichromene (CBC), ananti-inflammatory which may contribute to thepain-killing effect of cannabis.[37]
It takes over one hour for Marinol to reach full systemic effect,[38] compared to seconds or minutes forsmoked orvaporized cannabis.[39]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."[40]
Clinical trials comparing the use of cannabis extracts with Marinol in the treatment of cancercachexia have demonstrated equal efficacy and well-being among subjects in the two treatment arms.[41] United States federal law currently registers dronabinol as aSchedule III controlled substance, but all othercannabinoids remainSchedule I, except varioussynthetic cannabinoids likenabilone andHU-308.[42][43]
The FDA has recognized that there can be cannabinoid impurities in pharmaceutical dronabinol includingcannabinol,Δ8-Tetrahydrocannabinol,isotetrahydrocannabinol andΔ11-tetrahydrocannabinol.[44][45]
Initial rodent studies showed that injections of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, in the nodose ganglia suppressed serotonin induced reflex apneas and increased upper airway dilating muscle activity during sleep. Limited studies in humans with moderate-to-severe OSA have demonstrated significant reduction in AHI with dronabinol use.
This international non-proprietary name refers to only one of the stereochemical variants of delta-9-tetrahydrocannabinol, namely (−)-trans-delta-9-tetrahydrocannabinol
