Dear Editor:

Marijuana is one of the most common illegal drugs consumed in the United States. Its use is growing in popularity, especially among young people, partly because of increasing legalization, decriminalization, and the utility of medicinal marijuana.

Recreational marijuana differs from medical marijuana in that it has a higher concentration of tetrahydrocannabinol (THC). THC is the psychoactive component and has dependency potential. Medical marijuana has higher levels of cannabidiol (CBD) and has greater therapeutic value.[1]

There is a direct correlation between repeated, young-age cannabis exposure and white matter changes in the brain.[2] Marijuana use by children, adolescents, and young adults can result in abnormal neural development; long-term neurological deficits are also evident in those exposed prenatally.

Marijuana use during pregnancy has been reported to have a prevalence of nearly five percent in the United States.[3] Prenatal exposure is linked to neurobehavioral and cognitive impairments due to alteration of endocannabinoid signaling pathways, with weakening of fetal neuronal architecture. THC binding to cannabinoid-1 receptors during gestation alters central dopamine and opioid neurotransmitter system development, which regulates reward and motivation; it might also increase vulnerability to future drug abuse.4 In-utero exposure to THC might lead to fetal growth restriction and increased startle reflexes, tremors, impaired memory, and visual-motor discoordination in later-life.[3,4]

During adolescence, there is development of myelination, white matter tract formation, and neural connections.2 Cannabinoid receptors are abundant in brain, and long-term use of marijuana can negatively impact the brain by disturbing white matter connectivity. The neurodegeneration predominates in the frontal lobes, fornix, hippocampus, frontal-limbic connections, corpus callosum, and commissural fibers.2 Cannabis-induced alteration of frontal lobe white matter might lead to impulsivity and cognitive deficits. Marijuana consumption might also affect the cingulo-fronto-parietal cognitive attention network, responsible for executive control, inhibition, attention, and decision making.[2]

The corpus callosum, responsible for relaying information and directing inter-hemispheric communication, contains numerous cannabinoid receptors that are prone to damage from prolonged cannabis contact. This can result in loss of connecting fibers responsible for attentional and processing capabilities.[5]

Marijuana consumption in early life significantly affects neural maturation, jeopardizing educational, professional, and social achievements. Research on recurrent exposures has shown permanent ill-effects on memory, behavior, attention, and executive function.[6] Intellectual decline has been documented in young people who are chronic users of marijuana.

Only time and much more scientific research will reveal the true effects of marijuana on brain tissue and its functioning; there are studies that might refute potential dangers.[7,8] Nevertheless, educational programs for young people should be implemented to emphasize the theoretical dangers of marijuana exposure. Physicians should always provide guidance to their patients on marijuana use and its potential risks, particularly to young patients and those who are pregnant or are actively nursing their infants.

With regard,
Shivani Naik, MD; Murali Kolikonda, MD; Angeline Prabhu, MD; and Steven Lippmann, MD
Dr. Naik is a Research Scholar in the Department of Neurology, Dr. Kolikonda is a Neurology Resident in the Department of Neurology, Dr. Prabhu is a Research Scholar in the Department of Cardiology, and Dr. Lippmann is a Professor Emeritus in the Department of Psychiatry at University of Louisville, Louisville, Kentucky.

Funding/financial disclosures: The authors report no conflicts of interest relevant to the content of this letter.

References

  1. Kolikonda MK, Srinivasan K, Enja M, et al. Medical marijuana for epilepsy? Innov Clin Neurosci. 2016;13 (3–4):23–26.
  2. Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D. Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharmacol. 2011;19(3):231–242.
  3. Foeller ME, Lyell DJ. Marijuana use in pregnancy: concerns in an evolving era. J Midwifery Womens Health. 2017;62(3):363–367.
  4. Day NL, Goldschmidt L, Thomas CA. Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction. 2006;101(9):1313–1322.
  5. Arnone D, Barrick TR, Chengappa S, et al. Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. Neuroimage. 2008;41(3):1067–1074.
  6. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of National Academy of Science USA 2012; 109(40):2657–2664.
  7. Jackson NJ, Isen JD, Khoddam R, et al. Impact of adolescent marijuana use on intelligence: results from two longitudinal twin studies. Proc Nat Acd Sci. 2016;113(5). doi: 10.1073.
  8. Meier MH, Caspi A, Danese A, et al. Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study. Addiction. 2018;113(2); 257–265.