Do Not Be an Oblivious Drug Dealer: Part 1

Written with Ashley Stokes and Mary Claire Blackmon, PharmD Candidates 2017 at the Auburn University Harrison School of Pharmacy

It is estimated that 54 million people have used medications inappropriately at least once in their life.¹ Following alcohol and marijuana, prescription drugs and over-the-counter (OTC) drugs and supplements are the most commonly-abused substances in Americans aged 14 years and older. Drug abuse with OTC drugs can be misconceived as being safer than other illegal substances or prescription medications since they are sold without a prescription. Abuse of these agents are particularly popular with young people since they are readily accessible.¹

Smoking Alcohol

Smoking alcohol is alcohol (liquor, beer, etc.) that is vaporized by dry ice or pressure. When inhaled, the alcohol enters into the lungs and travels straight to the bloodstream.² The alcohol bypasses the stomach and liver, so it is not metabolized. The effects of alcohol are felt almost immediately. Furthermore, the protective mechanism of vomiting from excess alcohol is lost. This can increase the individual's risk of alcohol poisoning and alcohol-related death.³ Inhaling alcohol has been shown to be more addictive than drinking it. People trying to lose weight are trying this method to obtain the effects of alcohol without the calories. Smoked alcohol introduces the same dangerous interactions with prescription drugs as when orally ingested and patients who may be suspected of ingesting alcohol in this manner should be counseled appropriately.⁴

Nutmeg

Nutmeg is a commonly used food spice, originating from the Banda Islands in the Moluccas of Indonesia.⁵ Other than its role as a flavoring agent, nutmeg is used to make fragrances, essential oils, body butters, an abortifacient, an aphrodisiac, a larvicidal agent, and may serve as a substance of abuse.

For abusive purposes, it can be chewed or ground into a fine powder and drank with a beverage. It has intoxicating and psychoactive effects when taken in large amounts of greater than 20 grams, a little more than a tablespoon. It is estimated that between 5 and 20 grams (approximately 1 to 3 ground nutmeg seeds from a local farmer's’ market) are required to induce any kind of pharmacologic activity and that use of 1 to 2 milligram per kilogram of nutmeg can induce central nervous system (CNS) effects such as hallucinations.⁵ Gastrointestinal symptoms of nutmeg intoxication, such as nausea, vomiting, and diarrhea, can appear quickly within a half hour after ingestion. Then, roughly 3 to 8 hours later, hallucinogenic effects may begin, and last up to 48 hours. Other associated effects that may occur include anticholinergic effects, flushing, rapid heart rate, stupor, and convulsions.

The primary pharmacologic effects are speculated to be due to myristicin, a weak monoamine oxidase inhibitor found in nutmeg. It is chemically similar to mescaline, the active compound in peyote, which is a small desert cactus with a history of use in northern Mexico that produces auditory and visual hallucinations. It is believed that myristicin may be converted to MMDA, a psychomimetic amphetamine-like drug, in the liver. Effects of MMDA include euphoria, feelings of anxiety and loneliness, dizziness, and drowsiness. Myristicin is also active at serotonin receptors in the brain causing symptoms such as hypotension, sedation, and anesthesia.⁵ Myristicin is completely processed through the body within 48 hours, giving the agent such long-lasting effects. Another chemical found in nutmeg is elemicin. Elemicin is also active at serotonin receptors, and exhibits anti-depressive, hallucinogenic, and antihistaminic effects.

There have been 2 documented deaths from nutmeg intoxication. An 8-year-old boy fell into a coma and died 24 hours after ingesting 2 nutmegs (approximately 14 grams), the equivalent of 560 mg/kg of myristicin.⁶ The second case is of a 55-year-old woman, who was found with a mixture of flunitrazepam (Rohypnol) and myristicin in her blood. Blood tests revealed a dose of 560-840 mg/kg of myristicin and 0.072 mcg/ml of flunitrazepam.⁶ One to 3 ground nutmegs contains about 210 mg of myristicin and 70 mg of elemicin. These findings were confirmed post-mortem by UV-VIS spectroscopy and quantified by HPLC. Death was attributed to the combination of both substances.

Saffron

Saffron is the world’s most expensive spice at $11,000 per kilogram. It has been used throughout history for its color, smell, taste, and medicinal purposes. More recently, it comes as a supplement used for various proposed but unconfirmed health benefits.

The saffron stigmas, thread-like parts of the flower, contain 4 major bioactive ingredients: crocins, crocetin, picrocrocin, and safranal. Crocin has been shown to have serotonergic effects and has been proven to be as effective in depression in head-to-head trials with fluoxetine. For depression, the dose of saffron is one 30 mg supplement capsule daily for 6 to 8 weeks.⁷ However, saffron has been shown to have opioid-like effects that reduced reduced morphine withdrawal symptoms in mice.⁸ Finally, research has shown that saffron has a dose-dependent increase of dopamine and glutamate. For these properties, individuals are ingesting the saffron stigmas to obtain a high. Additionally, amounts greater than five grams (roughly one teaspoon) have uterine stimulant and abortifacient effects. High doses (12-20 grams or approximately one tablespoon) can be dangerous resulting in bleeding and/or death.⁷

Catnip

Catnip is a small plant of the mint family, native to parts of Asia, Europe, and China. Catnip is best known for the nature attraction that cats, both domestic and wild, exhibit toward the plant. To members of the feline family, catnip contains an attractant called nepetalactone, which causes feelings of relaxation, sleepiness, or anxiety when ingested by the cats.

For humans, catnip is usually brewed into an herbal tea, juice or tincture, used for smoking by drying out its leaves, used as a culinary herb, and appliced topically for arthritis and hemorrhoid treatment. Catnip has been used for its wide variety of medicinal qualities an antispasmodic, carminative, diaphoretic, and as a sedative. It is contraindicated in pregnancy due to uterine stimulating effects and abortifacient properties. Catnip is abused for its marijuana-like effects that are produced by drinking it in a beverage or smoking its leaves. Small doses of about 1.5 grams can last approximately 2 to 3 hours.⁹ Doses of 4 grams or more induce sedation. Unintended effects of catnip abuse are nausea, dizziness, and a mild hang-over feeling that typically subsides within a few hours. Lethal doses of catnip in humans has not yet been determined.

Actifed

Actifed is the combination of pseudoephedrine and triprolidine, an alkylamine antihistamine. It is abused for its pseudoephedrine component, which can be extracted by dissolving and filtering the ground up tablets to make methamphetamine. The drug increases the release of dopamine in the brain that is associated with euphoria and a rush feeling. Short-term side effects are wakefulness, rapid/irregular heart rate, and increased blood pressure. Long-term side effects include, severe dental problems, itching, anxiety, paranoia, hallucinations, stroke, heart attack, and death.¹

A case study has been published reporting paranoid psychosis after abusing Actifed. The amount consumed was one to two bottles over a 2-day period.⁹ In 2015, Nexafed was released as the only meth-deterring pseudoephedrine product. It contains special excipients that will polymerize when tampered with to create a thick gel.¹⁰ This is an excellent way for pharmacies to combat methamphetamine abuse.

Diphenhydramine

Diphenhydramine is inexpensive and easily accessible at drugstores. It has been shown to elevate mood, increase energy levels, and produce hallucinogenic effects. According to studies, doses of 300-700 mg, 12-28 diphenhydramine tablets or 120-280 ml of diphenhydramine liquid, are associated with hallucinogenic effects. Most abuse is from ingestion of the tablets; however, some abusers are particularly are fond of the gel capsules in which they can use for injection. The sedative side effect was thought to deter individuals from abusing it; however, there are reports that insomnia was actually experienced at higher doses. The anticholinergic action is associated with elevation of mood and hallucinogenic effects. Individuals will overdose on the diphenhydramine or combine it with other prescription drugs or alcohol to potentiate its effects. Other consequences of misuse are respiratory depression, altered mental status, gastrointestinal and cardiovascular effects.¹¹

Visine

Visine ophthalmic drops contain tetrahydrozoline, an alpha agonist. This drug can act on many different alpha-receptors to inhibit sympathetic outflow, decrease neuron activity, and CNS depression.¹² When Visine is ingested orally, it can produce drowsiness, coma, respiratory depression, and muscle flaccidity. In children 2-5 ml of 0.05% solution will produce coma. The dose in adults is unclear; a case report showed 30 ml of 0.05% Visine induced a light coma. The onset is 15 to 30 minutes and the duration of action is 12 to 24 hours. Due to its drowsiness and coma inducing, Visine is being used as a drug to facilitate sexual assault due to its solubility in drinks and tastelessness.¹³

Dramamine

Dramamine, or dimenhydrinate, is an over-the-counter medication used to treat motion sickness. It blocks histamine-1 receptors in the GI tract and the chemotrigger zone, and decreases vestibular stimulation. Dimenhydrinate is usually dosed at 50-100 mg per dose every four to six hours, with the maximum daily dose of 400 mg per day. Abusers seek the relaxing and sedative effects of the medication. But, when taken at high doses (exceeding 1 gram) this medication can cause delirium, amnesia, heart attacks, kidney problems and hallucinations.¹⁴ Dimenhydrinate has the potential to cause dependency. Abusers can experience tolerance after repeated use making it necessary to use higher and more dangerous doses to gain the sedative effects.¹⁴ Intoxication can be seen at doses ranging from 750-1250 mg, or 15-25 tablets, with the strong hallucinations and euphoria experienced at about 800 mg daily.¹⁴ The reported lethal dose of dimenhydrinate is variable, with cases of overdose and death at 25 mg/kg in adults.¹⁵ However, there is a case with an adult male ingesting 25 grams and developing torsades de pointes, but making a complete recovery.¹⁴ The first documented lethal overdose on dimenhydrinate occurred in 1993 when a 19-year-old woman ingested 5,000 mg, approximately one-hundred tablets, in less than one hour.¹⁴ The woman presented to the hospital in status epilepticus and having was experiencing ventricular arrhythmias. She experienced a severe neurologic deficit and minimal cerebral activity even after several attempts to stabilize her physiologic functions, and passed away after she was not able to recover.¹⁵

As pharmacists, there is an opportunity to intervene in the abuse of OTC drug abuse. Potential signs of abuse include large quantities bought and the leading population for store bought produce abuse is adolescents. If a certain drug is identified as being abused in the pharmacy, actions can be taken to keep the drug out of view or limit sales and restrict amount bought. An extreme measure could be to discontinue stocking the product. As always, it is your discretion to refuse the sale of a product to an individual suspected of abusing drugs. Addiction is a serious problem, which individuals need help. Be knowledgeable about local treatment centers to which you could refer individuals for recovery support.¹⁵

References

1. NIDA (2017). Drugs of Abuse. Retrieved April 5, 2017, from https://www.drugabuse.gov/drugs-abuse

2. Sifferlin A. Smoking alcohol: The Dangerous Way People are Getting Drunk. TIME Heathland. http://healthland.time.com/2013/06/05/smoking-alcohol-the-dangerous-way-people-are-getting-drunk/

3. Maclean RR, Valentine GW, Jatlow PI, Sofuoglu M. Inhalation of Alcohol Vapor: Measurement and Implications. Alcohol Clin Exp Res. 2017;41(2):238-250.

4. Tommasello AC. Substance abuse and pharmacy practice: what the community pharmacist needs to know about drug abuse and dependence. Harm Reduction Journal. 2004;1:3. doi:10.1186/1477-7517-1-3.

5. Dimenhydrinate [2017], Catnip [2017]. In: DRUGDEX® System (Micromedex 2.0). [AUHSOP Intranet]. Greenwood Village, CO: Truven Health Analytics Inc. [updated 2017, cited 2017 Apr 5]. Available from: http://www.micromedexsolutions.com/micromedex2/librarian/

6. Stein U, Greyer H, et al. Nutmeg (myristicin) poisoning — report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci International. 2001 Apr;118(1): 87-90.

7. Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, M. Tsatsakis A. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomedicine. 2015;5(5):376-391.

8. Hosseinzadeh H, Jahanian Z. Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice. Phytother Res. 2010;24(5):726-30.

9. Leighton KM. Paranoid psychosis after abuse of Actifed. BMJ (Clinical research ed). 1982;284(6318):789-790.

10. Nexafed. Acura Phamaceuticals, Inc. 2015. Retrieved April 5, 2017, from http://www.nexafed.com/references/

11. Thomas A, Nallur DG, Jones N, Deslandes PN. Diphenhydramine abuse and detoxification: a brief review and case report. J Psychopharmacol (Oxford). 2009;23(1):101-5.

12. Lev R, Clark RF. Visine Overdose: Case Report of an Adult with Hemodynamic Compromise. J Emer Med. 1995;13(5):649-52.

13. Spiller HA, Rogers J, Sawyer TS. Drug facilitated sexual assault using an over-the-counter ocular solution containing tetrahydrozoline (Visine). Leg Med (Tokyo). 2007;9(4):192-5.

14. Winn RE, McDonnell KP, et al. Fatality Secondary to Massive Overdose of Dimenhydrinate. Ann Emer Med. 1993; 22(9):1481-84.

15. Jessica Wright, Christine Bond, Helen D. Robertson, Catriona Matheson; Changes in over-the-counter drug misuse over 20 years: perceptions from Scottish pharmacists. J Public Health (Oxf). 2016; 38 (4): 793-799. doi: 10.1093/pubmed/fdv169