Marijuana Toxicity: An Increasing Clinical Challenge

As marijuana gains acceptance and becomes legal in some states for medical and/or recreational use, it is important to understand its effects on people and the toxicity associated with this drug.

Marijuana’s History

The history of recreational and medicinal use of marijuana dates back several thousand years. The hemp plant, cannabis sativa, became popular in the 1930’s and can be used to make rope, twine and fabric. It is also frequently used by people as a recreational drug. Hash oil is the most potent form of hemp’s extracts. The dried resins are referred to as hashish.

Of the 400 active compounds identified from the cannabis sativa plant, 60 active compounds have been grouped into a category called cannabinoids. The most psychoactive of these is delta-9-tetrahydrocannanbinol (THC) which produces feelings of relaxation, euphoria, increased sensory experience, changes in perception, analgesia and diminishing memory and concentration.

Marijuana’s Potency

Marijuana’s average THC potency has increased due to advances in plant breeding and management. Four decades ago, the average “joint” contained roughly 10 mg of THC. Today, the same marijuana cigarette contains closer to 60-150 mg. Because effects are generally dose-dependent, current marijuana users may encounter greater morbidity than those who used marijuana in the past.

Behavioral Effects of Using Marijuana

THC causes users to get “high.” It causes users to experience feelings of intoxication, detachment, relaxation, altered perception of time and distance, intensified sensory experience, laughter, talkativeness, diminished anxiety, dulled alertness, and mood depression. These effects are dose-dependent, but are also affected by the users’ expectations, mode of administration, peer activity and personality.

Dysphoric reactions to THC are commonly seen and may include panic, somatic sensations, mania, delirium, paranoia and, most frequently, significant anxiety. These reactions usually resolve without intervention.

Mental Effects of Using Marijuana

The most commonly observed effect of using marijuana is the impairment of one’s short-term memory. A subtle worsening of cognitive function has been identified in those who engage in chronic use of marijuana, the severity of which is dependent on the dosage and the duration of use. It is currently believed that in most cases, the cognitive deficits reverse themselves within one week after using the drug.

Cardiovascular Effects of Marijuana Use 

Some users experience a 20 to 100% increase in heart rate which can last from 60 to 180 minutes. THC can cause peripheral vasodilation and postural hypotension leading to syncope and dizziness. Overall cardiac output (which can increase up to 30%) may trigger ischemic events such as angina or infarction. There are scatted reports of congestive heart failure (CHF) and strokes being associated with THC intoxication.

Respiratory Effects of Marijuana Use

Transient bronchodilation has been observed in users of marijuana, as is typical with any inhaled substance. Increased sputum production, cough and bronchospasm are observed more frequently in patients with concurrent tobacco use. Several reports have suggested a link between cannabis smoking and cancer of the respiratory and digestive systems. Furthermore, a lot of illegally distributed marijuana contains Aspergillus, which can cause invasive pulmonary aspergillosis, particularly in immunocompromised patients.

How Marijuana Use Affects Reproductive Ability

High-dose THC causes a reduction in testosterone levels as well as a decrease in sperm motility, viability and production. Additionally, there are scattered clinical reports demonstrating the negative effects of THC on newborns and young children. Three studies have shown a possible risk of non-lymphoblastic leukemia, rhabdomyosarcoma as well as astrocytoma in children exposed to cannabis while in utero.

Marijuana Use Affects Metabolism and Elimination 

THC is metabolized by the hepatic cytochrome P450 system. Elimination half-life of THC can range from 2 to 57 hours after IV or inhalation exposure. Approximately 90% of THC is eliminated from the body in a little less than one week following exposure.

Marijuana’s Toxicity

Although the acute toxicity of marijuana is relatively benign in the average adult, such is not the case for children. A 250 to 1000 mg ingestion of hashish can result in unresponsiveness in one half hour. Pediatric apnea, cyanosis and bradycardia have been reported in children who have had exposure to the drug.

References:

1. Wells DL, Ott CA. The "new" marijuana. Ann Pharmacother. Mar 2011;45(3):414-7. [Medline].
2. Forrester MB. Adolescent synthetic cannabinoid exposures reported to Texas poison centers. Pediatr Emerg Care. Oct 2012;28(10):985-9. [Medline].
3. McGuinness TM, Newell D. Risky recreation: synthetic cannabinoids have dangerous effects. J Psychosoc Nurs Ment Health Serv. Aug 2012;50(8):16-8. [Medline].
4. Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. Mar 1 2011;342:d738. [Medline]. [Full Text].
5. Fitzgerald KT, Bronstein AC, Newquist KL. Marijuana poisoning. Top Companion Anim Med. Feb 2013;28(1):8-12. [Medline].
6. Wiegand TJ, Wax PM, Schwartz T, Finkelstein Y, Gorodetsky R, Brent J. The Toxicology Investigators Consortium Case Registry--the 2011 experience. J Med Toxicol. Dec 2012;8(4):360-77. [Medline].
7. National Institute on Drug Abuse, National Institutes of Health, Centers for Substance Abuse Prevention and Treatment. National Conference on Marijuana Use: Prevention, VA. Treatment and Research. NIH publication. 1995: Arlington;38-49:no 96-4106. [Full Text].
8. National Institute on Drug Abuse. InfoFacts: Marijuana. Updated April 2006. [Full Text].
9. Pavarin RM, Berardi D. Mortality risk in a cohort of subjects reported by authorities for cannabis possession for personal use. Results of a longitudinal study. Epidemiol Prev. Mar-Apr 2011;35(2):89-93. [Medline].
10. Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction. Nov 1996;91(11):1585-614. [Medline].
11. Ashton CH. Adverse effects of cannabis and cannabinoids. Br J Anaesth. Oct 1999;83(4):637-49. [Medline].
12. Ashton CH. Pharmacology and effects of cannabis: a brief review. Br J Psychiatry. Feb 2001;178:101-6. [Medline].
13. Compton WM, Grant BF, Colliver JD, Glantz MD, Stinson FS. Prevalence of marijuana use disorders in the United States: 1991-1992 and 2001-2002. JAMA. May 5 2004;291(17):2114-21. [Medline].
14. Degenhardt L, Hall W, Lynskey M. Exploring the association between cannabis use and depression. Addiction. Nov 2003;98(11):1493-504. [Medline].
15. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-60. [Medline].
16. Hall W, Solowij N. Adverse effects of cannabis. Lancet. Nov 14 1998;352(9140):1611-6. [Medline].
17. Hall W, Solowij N, Lemon J:. The Health and Psychological Consequences of Cannabis Use. Monograph No 25. National Drug Strategy. Australian Government Publication Serv. 1994;15-20.
18. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. Mar 1990;87(5):1932-6. [Medline].
19. Huestis MA, Mitchell JM, Cone EJ. Detection times of marijuana metabolites in urine by immunoassay and GC-MS. J Anal Toxicol. Oct 1995;19(6):443-9. [Medline].
20. Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Prog Neuropsychopharmacol Biol Psychiatry. Aug 2004;28(5):849-63. [Medline].
21. Khalsa JH, Genser S, Francis H, Martin B. Clinical consequences of marijuana. J Clin Pharmacol. Nov 2002;42(11 Suppl):7S-10S. [Medline].
22. Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP. Risk factors for adolescent substance abuse and dependence: data from a national sample. J Consult Clin Psychol. Feb 2000;68(1):19-30. [Medline].
23. Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA, Nelson EC, et al. Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA. Jan 22-29 2003;289(4):427-33. [Medline].
24. McGee R, Williams S, Poulton R, Moffitt T. A longitudinal study of cannabis use and mental health from adolescence to early adulthood. Addiction. Apr 2000;95(4):491-503. [Medline].
25. McGuigan M. Cannabinoids. In: Goldfrank's Toxicological Emergencies. 8^th ed. New York: McGraw-Hill Professional; 2006.
26. Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry. Oct 2001;58(10):909-15. [Medline].
27. Robson P. Cannabis. Arch Dis Child. Aug 1997;77(2):164-6. [Medline].
28. Smith NT. A review of the published literature into cannabis withdrawal symptoms in human users. Addiction. Jun 2002;97(6):621-32. [Medline].
29. Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, Miller M, et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA. Mar 6 2002;287(9):1123-31. [Medline].
30. Strang J, Witton J, Hall W. Improving the quality of the cannabis debate: defining the different domains. BMJ. Jan 8 2000;320(7227):108-10. [Medline].
31. Vitale S, van de Mheen D. Illicit drug use and injuries: A review of emergency room studies. Drug Alcohol Depend. Mar 15 2006;82(1):1-9. [Medline].
32. Wallace KL, Kunkel DB. Legal hemp products and urine cannabinoid testing. J Toxicol Clin Toxicol. 1999;37(7):897-8. [Medline].
33. Watson SJ, Benson JA Jr, Joy JE. Marijuana and medicine: assessing the science base: a summary of the 1999 Institute of Medicine report. Arch Gen Psychiatry. Jun 2000;57(6):547-52. [Medline].