1-테트라히드로칸나비놀

Biological Agents -> Plant Toxins

Stimulant

DEA NFLIS-Drug Category -> Cannabinoids

DEA NFLIS-Drug Category -> Cannabinoids

DEA NFLIS-Drug Category -> Cannabinoids

DEA Schedule II Controlled Substance -> Hallucinogenic substances

DEA Schedule III Controlled Substance -> Hallucinogenic substances

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

log Kow = 6.97

5.648

6.99

Light yellow resinous oil

Brown amorphous semi-solid, viscous oil or chunky golden yellow solid

2.8 mg/L at 73 °F (NTP, 1992)

In water, 2.8 mg/L at 23 °C

Essentially insoluble in water

1 part in 1 part of alcohol; 1 part in 1 part of acetone; 1 part in 3 parts of glycerol. In 0.15M sodium chloride, 0.77 mg/L at 23 °C. Soluble in fixed oils.

2.63e-03 g/L

Breast Feeding; Lactation; Milk, Human; Cannabinoids; Street Drugs

Breast Feeding; Lactation; Milk, Human; Antiemetics; Cannabinoids

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

392 °F at 0.02 mmHg (NTP, 1992)

BP: 200 °C at 0.02 mm Hg

1-trans-delta-9-tetrahydrocannabinol appears as brown amorphous semi-solid, viscous oil or chunky golden yellow solid. (NTP, 1992)

Light yellow oil; [Merck Index] Brown semi-solid, viscous liquid, or golden yellow solid; [CAMEO] Odorless resinous oil; [MSDSonline]

Solid

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 92 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

DEA schedule II controlled substance

DEA schedule III controlled substance

Regulation (EC) No 178/2002 (amended)

Delta-9-tetrahydrocannabinol: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

SYMPTOMS: Exposure to this compound may cause euphoria, relaxation, sleepiness, short term memory impairment; deterioration of ability to perform memory-dependent goal-oriented behavior, and loss of balance. Higher doses can cause hallucinations, delusions, paranoia, confusion, altered time sense, anxiety, nausea, vomiting, ataxia, stupor, coma, cardiovascular effects and redness of the eyes.

Emergency treatment: Plants- marijuana; Low level exposures cause mild euphoria and somnolence. Higher level exposures cause short term memory impairment, mood alterations, and decreased motor coordination. [HSDB] A respiratory tract irritant; [MSDSonline]

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Tetrahydrocannabinols (DEA Code Number: 7370) are included on this list. Meaning tetrahydrocannabinols naturally contained in a plant of the genus Cannabis (cannabis plant), as well as synthetic equivalents of the substances contained in the cannabis plant, or in the resinous extractives of such plant, and/or synthetic substances, derivatives, and their isomers with similar chemical structure and pharmacological activity to those substances contained in the plant, such as the following: 1 cis or trans tetrahydrocannabinol, and their optical isomers; 6 cis or trans tetrahydrocannabinol, and their optical isomers; and 3, 4 cis or trans tetrahydrocannabinol, and its optical isomers. (Since nomenclature of these substances is not internationally standardized, compounds of these structures, regardless of numerical designation of atomic positions covered.) /Tetrahydrocannabinols/

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Marihuana (DEA Code Number: 7360) is included on this list. /Marihuana/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Hallucinogenic substances. Dronabinol [(-)-delta-9-trans tetrahydrocannabinol] in an oral solution in a drug product approved for marketing by the U.S. Food and Drug Administration (DEA Code Number: 7365) is included on this list. /Dronabinol/

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Hallucinogenic substances. (1) Dronabinol (synthetic) in sesame oil and encapsulated in a soft gelatin capsule in a U.S. Food and Drug Administration approved product - /DEA Code Number:/ 7369. [Some other names for dronabinol: (6aR-trans)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol] or (-)-delta-9-(trans)-tetrahydrocannabinol]. /Dronabinol/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including dronabinol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dronabinol/

DHHS/NIDA; Research Monograph Series 79: Structure-Activity Relationships of the Cannabinoids p.177 (1987) DHHS Pub No. (ADM)90-1534

DHHS/NIDA; Research Monograph Series 14: Marijuana Research Findings p.130 (1976) DHHS Pub No. (ADM)81-1168

DHHS/NIDA; Research Monograph Series 50: Cocaine: Pharmacology Effects and Treatment of Abuse (1984) DHHS Pub No. ADM(87)-1326

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332

For more Special Reports (Complete) data for delta 9-Tetrahydrocannabinol (13 total), please visit the HSDB record page.

1-TRANS-DELTA-9-TETRAHYDROCANNABINOLis very unstable to light and high temperatures. It should be protected from air during all handling due to its extreme instability. (NTP, 1992). Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

Acute Tox. 4 (100%)

Acute Tox. 4 (100%)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Dronabinol Capsules, USP should be packaged in a well-closed container and stored in a refrigerator, 2 to 8 °C (36 to 46 °F). Protect from freezing.

When cannabis was stored at -18 °C, 4 °C, and 22 °C, the content of delta 9-tetrahydrocannabinol was reduced by 3.8, 5.3, and 6.9% respectively per year. There was greater deterioration at higher temperature.

Substantial amounts of THC (tetrahydrocanabinol) are lost from polystyrene, but not glass; vials when samples are stored at room temperature for 4 days and then frozen (-20 °C) for 4 wk.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

delta 9-Tetrahydrocannabinol was detected in 77 of 250 hair samples at <0.02-4.2 ng/mg(1). Cannabio shampoo contained 412 ng/mL of delta 9-tetrahydrocannabinol, delta 9-tetrahydrocannabinol was not detected (detection limit 0.05 ng/mg) in hair samples collected from individuals using this shampoo daily(2). About 70% of delta 9-tetrahydrocannabinol administered orally is excreted as its metabolites with 72 hours in feces and urine, only trace amounts of unmetabolized delta 9-tetrahydrocannabinol were detected in urine(2). Upon smoking cannabis cigarettes containing 1.75 and 3.55% delta 9-tetrahydrocannabinol, blood levels of delta 9-tetrahydrocannabinol were reported as 7 and 18.1 ng/mL, respectively(3). The half-life in blood was 18.7 hours to 4.1 days(3).

A potentially serious oral ingestion, if recent, should be managed with gut decontamination. In unconscious patients with a secure airway, instill activated charcoal (30 to 100 g in adults, 1 to 2 g/kg in infants) via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal. Patients experiencing depressive, hallucinatory or psychotic reactions should be placed in a quiet area and offered reassurance. Benzodiazepines (5 to 10 mg diazepam po) may be used for treatment of extreme agitation. Hypotension usually responds to Trendelenburg position and IV fluids. Pressors are rarely required. (L1712)

The cannabinoid receptor agonist delta(9)-tetrahydrocannabinol (THC) enhances the antinociceptive effects of u-opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on intravenous heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001-0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1-1.0 mg/kg) dose dependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032-0.032 mg/kg/infusion), heroin alone, or a mixture of THC and heroin. THC alone did not maintain responding above that obtained with saline; however, increasing the THC dose with heroin dose dependently decreased the number of infusions received and the rate of responding, as compared with data that were obtained with heroin alone. These results indicate that THC does not significantly enhance the positive reinforcing effects of heroin, further supporting the view that combining cannabinoid and opioid receptor agonists (e.g., for treating pain) does not increase, and might decrease, the abuse liability of individual drugs.

Although it is more common for drug abuse to progress from tobacco to cannabis, in many cases cannabis use develops before tobacco use. Epidemiological evidence indicates that prior cannabis use increases the likelihood of becoming dependent on tobacco. To determine whether this effect might be due to cannabis exposure per se, in addition to any genetic, social, or environmental factors that might contribute, we extended our series of studies on 'gateway drug' effects in animal models of drug abuse. Rats were exposed to THC, the main psychoactive constituent of cannabis, for 3 days (two intraperitoneal injections/day). Then, starting 1 week later, they were allowed to self-administer nicotine intravenously. THC exposure increased the likelihood of acquiring the nicotine self-administration response from 65% in vehicle-exposed rats to 94% in THC-exposed rats. When the price of nicotine was manipulated by increasing the response requirement, THC-exposed rats maintained higher levels of intake than vehicle-exposed rats, indicating that THC exposure increased the value of nicotine reward. These results contrast sharply with our earlier findings that prior THC exposure did not increase the likelihood of rats acquiring either heroin or cocaine self-administration, nor did it increase the reward value of these drugs. The findings obtained here suggest that a history of cannabis exposure might have lasting effects that increase the risk of becoming addicted to nicotine.

BACKGROUND: Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. METHODS: Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day-medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH. RESULTS: During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking. CONCLUSIONS: The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.

Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (delta9-tetrahydrocannabinol, delta9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of delta9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4x10 mg/kg, 2 hours apart) were pre- or post-treated with delta9-THC (1 or 3 mg/kg) and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP). Results showed that, as compared to corresponding controls (i) METH-induced nNOS overexpression in the caudate-putamen (CPu) was significantly attenuated by pre- and post-treatment with both doses of delta9-THC (-19% and -28% for 1 mg/kg pre- and post-treated animals; -25% and -21% for 3 mg/kg pre- and post-treated animals); (ii) METH-induced GFAP-immunoreactivity (IR) was significantly reduced in the CPu by post-treatment with 1 mg/kg delta9-THC1 (-50%) and by pre-treatment with 3 mg/kg delta9-THC (-53%); (iii) METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC) by pre- and post-treatment with both doses of delta9-THC (-34% and -47% for 1 mg/kg pre- and post-treated animals; -37% and -29% for 3 mg/kg pre- and post-treated animals). The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the delta9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our results indicate that delta9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.

For more Interactions (Complete) data for delta 9-Tetrahydrocannabinol (34 total), please visit the HSDB record page.

The heightened suggestibility and intensified emotions that hallucinogens create can worsen any pre-existing emotional problems. Physical effects of hallucinogen use include dilated pupils, sweating, insomnia, loss of appetite, tremors; and increased body temperature, heart rate and blood pressure.

Serum aminotransferase elevations during dronabinol therapy were reported to occur in 6% of treated patients compared to 4.3% in controls who receiving cancer chemotherapy. The aminotransferase elevations were transient, mild-to-moderate in severity, and not associated with symptoms or jaundice. There have been no convincing cases of clinically apparent liver injury attributable to dronabinol published in the literature and, thus, significant liver injury from dronabinol must be exceeding rare, if it occurs at all.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 330,000(SRC), determined from a structure estimation method(2), indicates that delta 9-tetrahydrocannabinol is expected to be immobile in soil(SRC). Volatilization of delta 9-tetrahydrocannabinol from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(2). delta 9-Tetrahydrocannabinol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.8X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 330,000(SRC), determined from a structure estimation method(2), indicates that delta 9-tetrahydrocannabinol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). delta 9-Tetrahydrocannabinol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 18,000(SRC), from its log Kow of 6.97(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), delta 9-tetrahydrocannabinol, which has an estimated vapor pressure of 4.6X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase delta 9-tetrahydrocannabinol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 75 minutes(SRC), calculated from its rate constant of 3.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). The rate constant for the vapor-phase reaction of delta 9-tetrahydrocannabinol with ozone has been estimated as 4.3X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). This corresponds to an atmospheric half-life of about 38 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(3). Particulate-phase delta 9-tetrahydrocannabinol may be removed from the air by wet and dry deposition(SRC). delta 9-Tetrahydrocannabinol absorb light at a maximum wavelength of 283 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Neurotoxin - Other CNS neurotoxin

The most commonly reported adverse effects of THC usage that necessitate discontinuation are dysphoria, hallucinations, and paranoia. Other prevalent adverse effects include sedation, confusion, headache, dry mouth, euphoria, and hypotension. In addition, seizures and seizure-like activity have been reported in patients using THC.

Hypersensitivity to Dronabinol or Sesame Oil: Clinical staff should monitor patients for signs of hypersensitivity reactions. Reported signs include lip swelling, hive, rash, oral lesions, skin burning, and throat tightness.

IDENTIFICATION AND USE: delta 9-tetrahydrocannabinol (THC, dronabinol) is light yellow resinous oil. This is a Schedule I controlled substance in the USA. The only legal medical application for marijuana is to reduce the adverse effects of chemotherapy for cancer patients, some patients have been given THC to reduce the pressure in the eye from glaucoma. HUMAN STUDIES: An oral dose of 20 mg of delta-9-THC or the smoking of a cigarette containing 2% delta-9-THC produces effects on mood, memory, motor coordination, cognitive ability, sensorium, time sense, and self-perception. Most commonly there is an increased sense of well-being or euphoria, accompanied by feelings of relaxation and sleepiness when subjects are alone; where users can interact, sleepiness is less pronounced and there is often spontaneous laughter. Short-term memory is impaired, and there is a deterioration in capacity to carry out tasks requiring multiple mental steps to reach a specific goal. High doses of delta 9-THC can induce frank hallucinations, delusions, and paranoid feelings. Thinking becomes confused and disorganized; depersonalization and altered time sense are accentuated. Anxiety reaching panic proportions may replace euphoria, often as a result of the feeling that the drug-induced state will never end. With high enough doses, the clinical picture is that of a toxic psychosis with hallucinations, depersonalization, and loss of insight; this can occur acutely or only after months of use. Clinical manifestations due to marijuana smoking have included long-term impairment of memory in adolescents, a sixfold increase in the incidence of schizophrenia, cancer of the mouth, jaw, tongue, and lungs in 19- to 30-year olds, fetotoxicity, and nonlymphoblastic leukemia in children of marijuana-smoking mothers. Studies of aircraft pilot performance following the smoking of one cigarette containing 20 mg of THC suggest that impairment of performance can last as long as 24 hours after smoking. The user may be unaware of the drug's influence. Babies born to mothers who smoked marijuana during pregnancy weighed an average of 3.4 ounces less than babies born to a control group of mothers who did not smoke marijuana; there was no statistically significant difference in either gestational age or frequency of congenital abnormalities. ANIMAL STUDIES: There was no evidence of carcinogenic activity of 1-trans-delta 9-tetrahydrocannabinol in male or female rats administered 12.5, 25, or 50 mg/kg. There was equivocal evidence of carcinogenic activity of THC in male and female mice based on the increased incidences of thyroid gland follicular cell adenomas in 125 mg/kg groups. Increased incidences of thyroid gland follicular cell hyperplasia occurred in male and female mice, and increased incidences of hyperplasia and ulcers of the forestomach were observed in male mice. The incidences of mammary gland fibroadenomas and uterine stromal polyps were decreased in dosed groups of female rats, as were the incidences of pancreatic adenomas, pituitary gland adenomas, and interstitial cell adenomas of the testis in dosed male rats and liver neoplasms in dosed mice. In a long-term study (77 days) in rats, oral administration of dronabinol at doses of 30 to 150 mg/sq m reduced ventral prostate, seminal vesicle and epididymal weights and caused a decrease in seminal fluid volume. Decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testis were also observed. However, sperm count, mating success and testosterone levels were not affected. Dronabinol was not genotoxic in the Ames tests, the in vitro chromosomal aberration test in Chinese hamster ovary cells, and the in vivo mouse micronucleus test. It, however, produced a weak positive response in a sister chromatid exchange test in Chinese hamster ovary cells. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms.

The median lethal dose (LD50) of THC has been determined in various animal species through oral administration and ranges from 800 to 9000 mg/kg. In humans, there have been no recorded instances of fatal overdoses resulting from acute THC use. However, estimates for a potentially lethal human dose range from 4 to 15 g.

Toxicity

The mechanism of action of marinol is not completely understood. It is thought that cannabinoid receptors in neural tissues may mediate the effects of dronabinol and other cannabinoids. Animal studies with other cannabinoids suggest that marinol's antiemetic effects may be due to inhibition of the vomiting control mechanism in the medulla oblongata.

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Tetrahydrocannabinols (DEA Code Number: 7370) are included on this list. Meaning tetrahydrocannabinols naturally contained in a plant of the genus Cannabis (cannabis plant), as well as synthetic equivalents of the substances contained in the cannabis plant, or in the resinous extractives of such plant, and/or synthetic substances, derivatives, and their isomers with similar chemical structure and pharmacological activity to those substances contained in the plant, such as the following: 1 cis or trans tetrahydrocannabinol, and their optical isomers; 6 cis or trans tetrahydrocannabinol, and their optical isomers; and 3, 4 cis or trans tetrahydrocannabinol, and its optical isomers. (Since nomenclature of these substances is not internationally standardized, compounds of these structures, regardless of numerical designation of atomic positions covered.) /Tetrahydrocannabinols/

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Marihuana (DEA Code Number: 7360) is included on this list. /Marihuana/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Hallucinogenic substances. Dronabinol [(-)-delta-9-trans tetrahydrocannabinol] in an oral solution in a drug product approved for marketing by the U.S. Food and Drug Administration (DEA Code Number: 7365) is included on this list. /Dronabinol/

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Hallucinogenic substances. (1) Dronabinol (synthetic) in sesame oil and encapsulated in a soft gelatin capsule in a U.S. Food and Drug Administration approved product - /DEA Code Number:/ 7369. [Some other names for dronabinol: (6aR-trans)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol] or (-)-delta-9-(trans)-tetrahydrocannabinol]. /Dronabinol/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including dronabinol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dronabinol/

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

Dronabinol-induced sympathomimetic activity may result in tachycardia and/or conjunctival injection. Its effects on blood pressure are inconsistent, but subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing. Dronabinol also demonstrates reversible effects on appetite, mood, cognition, memory, and perception. These phenomena appear to be dose-related, increasing in frequency with higher dosages, and subject to great inter-patient variability. After oral administration, dronabinol capsules have an onset of action of approximately 0.5 to 1 hour and a peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of dronabinol may continue for 24 hours or longer after administration. Tachyphylaxis and tolerance develop to some of the cardiovascular and CNS pharmacologic effects of dronabinol with chronic use, suggesting an indirect effect on sympathetic neurons. In a study of the pharmacodynamics of chronic dronabinol exposure, healthy male subjects (N = 12) received 12 times the maximum dose for anorexia associated with weight loss in patients with AIDS of dronabinol capsules in divided doses for 16 days. An initial tachycardia induced by dronabinol was replaced successively by normal sinus rhythm and then bradycardia. A decrease in supine blood pressure, made worse by standing, was also observed initially. These subjects developed tolerance to the cardiovascular and subjective adverse CNS effects of dronabinol within 12 days of treatment initiation. Tachyphylaxis and tolerance do not appear to develop to the appetite stimulant effect of dronabinol. In clinical studies of dronabinol capsules in AIDS patients, at the recommended dosage, the appetite stimulant effect was sustained for up to five months.

Dronabinol is a synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). THC demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, which results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes.

The availability of potent synthetic agonists for cannabinoid receptors has facilitated our understanding of cannabinoid actions on synaptic transmission in the central nervous system. Moreover, the ability of these compounds to inhibit neurotransmitter release at many central synapses is thought to underlie most of the behavioral effects of cannabinoid agonists. However, despite the widespread use and misuse of marijuana, and recognition of its potential adverse psychological effects in humans, comparatively few studies have examined the actions of its primary psychoactive constituent, delta(9)-tetrahydrocannabinol (THC), at well-defined synaptic pathways. Here we examine the recent literature describing the effects of acute and repeated THC exposure on synaptic function in several brain regions and explore the importance of these neurobiological actions of THC in drug addiction.

Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V max (complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), V tmpd (complex IV activity), together with mitochondrial coupling (V max/V 0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased V max (-71%; P<0.0001), V succ (-65%; P<0.0001), and V tmpd (-3.5%; P<0.001). Mitochondrial coupling (V max/V 0) was also significantly decreased after THC exposure (1.8+/-0.2 versus 6.3+/-0.7; P<0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05) and mitochondrial free radical leak was increased from 0.01+/-0.01 to 0.10+/-0.01% (P<0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke.

MDSCs are potent immunosuppressive cells that are induced during inflammatory responses, as well as by cancers, to evade the antitumor immunity. We recently demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the current study, we investigated the epigenetic mechanisms through which THC, an exogenous cannabinoid, induces MDSCs and compared such MDSCs with the naive MDSCs found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs, which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore, promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs, and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding protein associated with accumulation of MDSCs in cancer models. Neutralization of S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the suppressive function of MDSCs. Together, the current study demonstrates that THC mediates epigenetic changes to promote MDSC differentiation and function and that S100A8 plays a critical role in this process.

Dronabinol is an orally active cannabinoid which, like other cannabinoids, has complex effects on the central nervous system (CNS), including central sympathomimetic activity. Cannabinoid receptors have been discovered in neural tissues. These receptors may play a role in mediating the effects of dronabinol and other cannabinoids.

For more Mechanism of Action (Complete) data for delta 9-Tetrahydrocannabinol (10 total), please visit the HSDB record page.

The elimination phase of dronabinol can be described using a two-compartment model with an initial (alpha) half-life of about 4 hours and a terminal (beta) half-life of 25 to 36 hours.

The elimination phase of dronabinol can be described using a two compartment model with an initial (alpha) half-life of about 4 hours and a terminal (beta) half-life of 25 to 36 hours.

After the pseudo-equilibrium is reached, THC is then slowly eliminated. This slow elimination is primarily due to the slow return of THC from sequestered tissues to blood. The terminal half-life of THC is approximately 1 day. /Several investigators have/ suggested terminal half-life /ranging between/ 19 to 36 hours. There are no significant differences in plasma profiles for chronic and infrequent users or in half-lives in moderate users before and after a 2-week exposure of THC.

The elimination half-life of dronabinol (delta-1-tetrahydrocannabinol) in 3 chronic marihuana users following smoking 4 cigarettes over a 2 day period is reported. The elimination half-life in blood plasma was calculated to be 4.1 days (range 2.9-5.0 days).

The terminal plasma half-life of metabolites from THC administration is approximately 50 hours, which is longer than that of THC. ... /Metabolites/

THC is primarily metabolized in the liver by microsomal hydroxylation and oxidation reactions catalyzed by Cytochrome P450 enzymes. 11-hydroxy-▵9-tetrahydrocannabinol (11-OH-THC) is the primary active metabolite, capable of producing psychological and behavioural effects, which is then metabolized into 11-nor-9-carboxy-▵ 9-tetrahydrocannabinol (THC-COOH), THC's primary inactive metabolite. Dronabinol and its principal active metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma. Concentrations of both parent drug and metabolite peak at approximately 0.5 to 4 hours after oral dosing and decline over several days.

The analgesic activity of delta-8- and delta-9-THC is mainly due to the 11-hydroxy metabolite.

The metabolism of delta(9)-tetrahydrocannabinol (THC) is relatively complex, and over 80 metabolites have been identified. However, much less is known about the formation and fate of cannabinoid conjugates. Bile excretion is known to be an important route for the elimination of phase II metabolites. A liquid chromatography-tandem mass spectrometry LC-MS/MS procedure for measuring cannabinoids in oral fluid was adapted, validated and applied to 10 bile samples. THC, 11-hydroxy-delta(9)-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol (THCCOOH), cannabinol (CBN), cannabidiol (CBD), delta(9)-tetrahydrocannabinolic acid A (THC-A), 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol glucuronide (THCCOOH-gluc) and delta(9)-tetrahydrocannabinol glucuronide (THC-gluc) were determined following solid-phase extraction and LC-MS/MS. High concentrations of THCCOOH-gluc were found in bile samples (range: 139-21,275 ng/mL). Relatively high levels of THCCOOH (7.7-1548 ng/mL) and THC-gluc (38-1366 ng/mL) were also measured. THC-A, the plant precursor of THC, was the only cannabinoid that was not detected. These results show that biliary excretion is an important route of elimination for cannabinoids conjugates and that their enterohepatic recirculation is a significant factor to consider when analyzing blood elimination profiles of cannabinoids. Furthermore, we suggest that the bile is the matrix of choice for the screening of phase II cannabinoid metabolites.

The presence of the metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (C-THC) in hair is generally accepted as the definitive proof of delta-9-tetrahydrocannabinol (THC) ingestion. During hair analysis, the removal of any potential C-THC external contamination that could result from marijuana smoke or close personal contact via a wash procedure is critical. Here, we performed a series of experiments to demonstrate that C-THC is the reliable indicator of marijuana ingestion when paired with the correct washing procedure to remove potential external contamination.

Dronabinol undergoes extensive first-pass hepatic metabolism, primarily by microsomal hydroxylation, yielding both active and inactive metabolites. Dronabinol and its principal active metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma.

For more Metabolism/Metabolites (Complete) data for delta 9-Tetrahydrocannabinol (15 total), please visit the HSDB record page.

7J8897W37S

DRONABINOL

Established Pharmacologic Class [EPC] - Cannabinoid

Chemical Structure [CS] - Cannabinoids

Dronabinol is a Cannabinoid.

DRONABINOL

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.

A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents).

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.

Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.

Dronabinol is almost completely absorbed (90 to 95%) after a single oral dose. Due to the combined effects of first-pass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches systemic circulation. Relative bioavailability data from healthy male and female subjects suggest that a dose of 4.2 mg of SYNDROS provides comparable systemic exposure (Cmax and AUC) to a 5 mg dronabinol capsule, under fasted conditions, with the Cmax and AUCinf of 1.9 ± 1.3 ng/mL and 3.8 ± 1.8 ng.h/mL respectively. The concentrations of both dronabinol and its major active metabolite (11-hydroxy-delta-9-THC) peak at approximately 0.5 to 4 hours after oral dosing with SYNDROS and decline over several days. The mean inter- and intra-subject variability in dronabinol pharmacokinetics (Cmax and AUCinf) was approximately 66% and 47% and 67% and 14%, respectively, following the administration of SYNDROS to healthy subjects.

Dronabinol and its biotransformation products are excreted in both feces and urine. Biliary excretion is the major route of excretion with about half of a radiolabeled oral dose being recovered from the feces within 72 hours as contrasted with 10 to 15% recovered from urine. Less than 5% of an oral dose is recovered unchanged in the feces. Due to its redistribution, dronabinol and its metabolites may be excreted for prolonged periods of time. Following single-dose administration, dronabinol metabolites have been detected for more than 5 weeks in the urine and feces. In a study of dronabinol capsules involving AIDS patients, urinary cannabinoid/creatinine concentration ratios were studied bi-weekly over a six-week period. The urinary cannabinoid/creatinine ratio was closely correlated with the dose. No increase in the cannabinoid/creatinine ratio was observed after the first two weeks of treatment, indicating that steady-state cannabinoid levels had been reached. This conclusion is consistent with predictions based on the observed terminal half-life of dronabinol.

Dronabinol has a large apparent volume of distribution, approximately 10 L/kg, because of its lipid solubility.

The value for clearance average is about 0.2 L/kg-hr but is highly variable due to the complexity of cannabinoid distribution.

To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 hr after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 ug/L for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 ug/L, respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD < 15%). The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies. Pharmacokinetic parameters of THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 00.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51226.00 and 68031.48 mg/L x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L/min x kg. Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 hr), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

/MILK/ Marijuana has not been well studied, but tetrahydrocannabinol can reach rather high levels in /breast/ milk, particularly with heavy use. Although adverse effects in infants have not been reported, breast feeding should probably be avoided in heavy users and during therapeutic dronabinol use. Breast feeding should probably be withheld for several hr after occasional marijuana use. Caution should also be used to avoid exposing the infant to marijuana smoke.

The primary psychoactive component of cannabis; Used therapeutically as antiemetic and appetite stimulant; [Merck Index]

Tetrahydrocannabinols (DEA Code Number: 7370) is a Schedule I contolled substance. /Tetrahydrocannabinols/

Marihuana (DEA Code Number: 7360) is a Schedule I controlled substance. /Marihuana/

Dronabinol [(-)-delta-9-trans tetrahydrocannabinol] in an oral solution in a drug product approved for marketing by the U.S. Food and Drug Administration (DEA Code Number: 7365) is a Schedule II controlled substance. /Dronabinol/

In some EU countries there is licensed cultivation of cannabis for fiber production (hemp), but the THC content of these plants is less than 0.3%.

For more Uses (Complete) data for delta 9-Tetrahydrocannabinol (6 total), please visit the HSDB record page.

Annual marijuana use among young adults age 18-25: 34.2% (1974); 35.0% (1976); 38.7% (1977); 46.9% (1979); 40.4% (1982); 36.9% (1985); 27.9% (1988); 24.6% (1990) /From table/

Annual marijuana use among adults age 26 or older: 3.8% (1974); 5.4% (1976); 6.4% (1977); 9.0% (1979); 10.6% (1982); 9.5% (1985); 6.9% (1988); 7.3% (1990) /From table/

Cannabis is a natural product, the main psychoactive constituent of which is tetrahydrocannabinol (delta9-THC). The cannabis plant (Cannabis sativa L.) is broadly distributed and grows in temperate and tropical areas. ... Herbal cannabis consists of the dried flowering tops and leaves. Cannabis resin is a compressed solid made from the resinous parts of the plant, and cannabis (hash) oil is a solvent extract of cannabis.

Common street names include: Aunt Mary, BC Bud, Blunts, Boom, Chronic, Dope, Gangster, Ganja, Grass, Hash, Herb, Hydro, Indo, Joint, Kif, Mary Jane, Mota, Pot, Reefer, Sinsemilla, Skunk, Smoke, Weed, and Yerba

Common street names include: * 710 (the word "OIL" flipped and spelled backwards), wax, ear wax, honey oil, budder, butane hash oil, butane honey oil (BHO), shatter, dabs (dabbing), black glass, and errl. /Marijuana concentrates/

In 2011, cannabis resin at retail level in Europe was reported to have an average THC content that varied from 4% (Hungary) to 16% (The Netherlands), while herbal cannabis potency ranged from 1% (Hungary) to 16% (The Netherlands) ... Herbal cannabis produced by intensive indoor methods may have an average potency two or three times greater than that of imported herbal cannabis, although the two overlap.

Table: Dronabinol Preparations [Table#6015]

For more Formulations/Preparations (Complete) data for delta 9-Tetrahydrocannabinol (6 total), please visit the HSDB record page.

The major active principle in all cannabis products is delta9- tetrahydrocannabinol (delta9-THC or simply THC), also known by its International Non-Proprietary Name (INN) as dronabinol. The unsaturated bond in the cyclohexene ring is located between C-9 and C-10 in the more common dibenzopyran ring numbering system. There are four stereoisomers of THC, but only the (-)-trans isomer occurs naturally (CAS-1972-08-03). The fully systematic name for this THC isomer is (-)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol. Two related substances, delta9- tetrahydrocannabinol-2-oic acid and delta9-tetrahydrocannabinol-4-oic acid (THCA), are also present in cannabis, sometimes in large amounts. During smoking, THCA is partly converted to THC. The active isomer delta8-THC, in which the unsaturated bond in the cyclohexene ring is located between C-8 and C-9, is found in much smaller amounts.

Marinol, /is/ a synthetic version of THC, the active ingredient found in the marijuana plant.

Cannabis is a natural product, the main psychoactive constituent of which is tetrahydrocannabinol (delta9-THC). The cannabis plant (Cannabis sativa L.) is broadly distributed and grows in temperate and tropical areas. ... Herbal cannabis consists of the dried flowering tops and leaves. Cannabis resin is a compressed solid made from the resinous parts of the plant, and cannabis (hash) oil is a solvent extract of cannabis.

Cannabis sativa is dioecious: there are separate male and female plants. The THC is largely concentrated around the flowering parts of the female plant. The leaves and male plants have less THC, while the stalks and seeds contain almost none.

For more General Manufacturing Information (Complete) data for delta 9-Tetrahydrocannabinol (7 total), please visit the HSDB record page.