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Try out PMC Labs and tell us what you think. Learn More. In light of the rapidly shifting landscape regarding the legalization of marijuana for medical and recreational purposes, patients may be more likely to ask physicians about its potential adverse and beneficial effects on health. The popular notion seems to be that marijuana is a harmless pleasure, access to which should not be regulated or considered illegal.
Hashish is a related product created from the resin of marijuana flowers and is usually smoked by itself or in a mixture with tobacco but can be ingested orally. Marijuana can also be used to brew tea, and its oil-based extract can be mixed into food products. The regular use of marijuana during adolescence is of particular concern, since use by this age group is associated with an increased likelihood of deleterious consequences 2 Table 1. Although multiple studies have reported detrimental effects, others have not, and the question of whether marijuana is harmful remains the subject of heated debate.
Here we review the current state of the science related to the adverse health effects of the recreational use of marijuana, focusing on those areas for which the evidence is strongest. Despite some contentious discussions regarding the addictiveness of marijuana, the evidence clearly indicates that long-term marijuana use can lead to addiction. There is also recognition of a bona fide cannabis withdrawal syndrome 5 with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxietywhich makes cessation difficult and contributes to relapse.
Marijuana use by adolescents is particularly troublesome. The brain remains in a state of active, experience-guided development from the prenatal period through childhood and adolescence until the age of approximately 21 years.
This view has received considerable support from studies in animals, which have shown, for example, that prenatal or adolescent exposure to THC can recalibrate the sensitivity of the reward system to other drugs 10 and that prenatal exposure interferes with cytoskeletal dynamics, which are critical for the establishment of axonal connections between neurons.
As compared with unexposed controls, adults who smoked marijuana regularly during adolescence have impaired neural connectivity fewer fibers in specific brain regions. These include the precuneus, a key node that is involved in functions that require a high degree of integration e. One study showed that selective down-regulation of cannabinoid-1 CB1 receptors in several cortical brain regions in long-term marijuana smokers was correlated with years of cannabis smoking and was reversible after 4 weeks of abstinence. The negative effect of marijuana use on the functional connectivity of the brain is particularly prominent if use starts in adolescence or young adulthood, 12 which may help to explain the finding of an association between frequent use of marijuana from adolescence into adulthood and ificant declines in IQ.
Epidemiologic and preclinical data suggest that the use of marijuana in adolescence could influence multiple addictive behaviors in adulthood. Regular marijuana use is associated with an increased risk of anxiety and depression, 23 but causality has not been established. Marijuana is also linked with psychoses including those associated with schizophreniaespecially among people with a preexisting genetic vulnerability, 24 and exacerbates the course of illness in patients with schizophrenia. Heavier marijuana use, greater drug potency, and exposure at a younger age can all negatively affect the disease trajectory e.
However, it is inherently difficult to establish causality in these types of studies because factors other than marijuana use may be directly associated with the risk of mental illness. In addition, other factors could predispose a person to both marijuana use and mental illness. This makes it difficult to confidently attribute the increased risk of mental illness to marijuana use. In the Monitoring the Future survey of high-school students, 26 6. Although acute effects may subside after THC is cleared from the brain, it nonetheless poses serious risks to health that can be expected to accumulate with long-term or heavy use.
The evidence suggests that such use in measurable and long-lasting cognitive impairments, 16 particularly among those who started to use marijuana in early adolescence. Moreover, failure to learn at school, even for short or sporadic periods a secondary effect of acute intoxicationwill interfere with the subsequent capacity to achieve increasingly challenging educational goals, a finding that may also explain the association between regular marijuana use and poor grades.
The relationship between cannabis use by young people and psychosocial harm is likely to be multifaceted, which may explain the inconsistencies among studies. For example, some studies suggest that long-term deficits may be reversible and remain subtle rather than disabling once a person abstains from use. Heavy marijuana use has been linked to lower income, greater need for socioeconomic assistance, unemployment, criminal behavior, and lower satisfaction with life. Both immediate exposure and long-term exposure to marijuana impair driving ability; marijuana is the illicit drug most frequently reported in connection with impaired driving and accidents, including fatal accidents.
Recent marijuana smoking and blood THC levels of 2 to 5 ng per milliliter are associated with substantial driving impairment. The effects of long-term marijuana smoking on the risk of lung cancer are unclear. For example, the use of marijuana for the equivalent of 30 or more t-years with 1 t-year of marijuana use equal to 1 cigarette [t] of marijuana smoked per day for 1 year was associated with an increased incidence of lung cancer and several cancers of the upper aerodigestive tract; however, the association disappeared after adjustment for potential confounders such as cigarette smoking.
Marijuana smoking is also associated with inflammation of the large airways, increased airway resistance, and lung hyperinflation, associations that are consistent with the fact that regular marijuana smokers are more likely to report symptoms of chronic bronchitis than are nonsmokers 42 ; however, the long-term effect of low levels of marijuana exposure does not appear to be ificant.
However, the direct effects of cannabinoids on various target receptors i. Most of the long-term effects of marijuana use that are summarized here have been observed among heavy or long-term users, but multiple often hidden confounding factors detract from our ability to establish causality including the frequent use of marijuana in combination with other drugs. These factors also complicate our ability to assess the true effect of intrauterine exposure to marijuana.
Indeed, despite the use of marijuana by pregnant women, 48 and animal models suggesting that cannabis exposure during pregnancy may alter the normal processes and trajectories of brain development, 49 our understanding of the long-term effects of prenatal exposure to marijuana in humans is very poor. This increase in THC content raises concerns that the consequences of marijuana use may be worse now than in the past and may for the ificant increases in emergency department visits by persons reporting marijuana use 51 Fig.
Panel A shows the increasing potency of marijuana i. There is also a need to improve our understanding of how to harness the potential medical benefits of the marijuana plant without exposing people who are sick to its intrinsic risks. The authoritative report by the Institute of Medicine, Marijuana and Medicine52 acknowledges the potential benefits of smoking marijuana in stimulating appetite, particularly in patients with the acquired immunodeficiency syndrome AIDS and the related wasting syndrome, and in combating chemotherapy-induced nausea and vomiting, severe pain, and some forms of spasticity.
The report also indicates that there is some evidence for the benefit of using marijuana to decrease intraocular pressure in the treatment of glaucoma. Nonetheless, the report stresses the importance of focusing research efforts on the therapeutic potential of synthetic or pharmaceutically pure cannabinoids. This practice raises particular concerns with regard to long-term use by vulnerable populations.
For example, there is some evidence to suggest that in patients with symptoms of human immunodeficiency virus HIV infection or AIDS, marijuana use may actually exacerbate HIV-associated cognitive deficits. Early evidence of the benefits of marijuana in patients with glaucoma a disease associated with increased pressure in the eye may be consistent with its ability to effect a transient decrease in intraocular pressure, 5354 but other, standard treatments are currently more effective. THC, cannabinol, and nabilone a synthetic cannabinoid similar to THCbut not cannabidiol, were shown to lower intraocular pressure in rabbits.
Treatment of the nausea and vomiting associated with chemotherapy was one of the first medical uses of THC and other cannabinoids. Other, unidentified compounds in marijuana may enhance the effect of THC as appears to be the case with THC and cannabidiol, which operate through different antiemetic mechanisms.
Reports have indicated that smoked or ingested cannabis improves appetite and le to weight gain and improved mood and quality of life among patients with AIDS. Marijuana has been used to relieve pain for centuries. Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors, 63 play important roles in modeling nociceptive responses in various models of pain.
These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain, 6465 even at very low levels of THC 1. Cannabinoids e. Nabiximols Sativex, GW Pharmaceuticalsan oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis.
Sativex is available in the United Kingdom, Canada, and several other countries 7071 and is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanicals for the treatment of epilepsy. Research is needed on the ways in which government policies on marijuana affect public health outcomes. Our understanding of the effects of policy on market forces is quite limited e.
Historically, there has been an inverse correlation between marijuana use and the perception of its risks among adolescents Fig. Assuming that this inverse relationship is causal, would greater permissiveness in culture and social policy lead to an increase in the of young people who are exposed to cannabis on a regular basis?
Among students in grade 12, the reported prevalence of regular marijuana smoking has been steadily increasing in recent years and may soon intersect the trend line for regular tobacco smoking Fig. We also need information about the effects of second-hand exposure to cannabis smoke and cannabinoids. Second-hand exposure is an important public health issue in the context of tobacco smoking, but we do not have a clear understanding of the effects of second-hand exposure to marijuana smoking.
Panel A shows the inverse correlation between the perception of the risk associated with marijuana use and actual use. Perceived risk corresponds to the percentage of teenagers who reported that the use of marijuana is dangerous. Panel B shows the percentage of students who reported daily use of tobacco cigarettes or marijuana in the 30 days.
Data for both graphs are from Johnston et al. Marijuana use has been associated with substantial adverse effects, some of which have been determined with a high level of confidence Table 2. Marijuana, like other drugs of abuse, can result in addiction. During intoxication, marijuana can interfere with cognitive function e. Repeated marijuana use during adolescence may result in long-lasting changes in brain function that can jeopardize educational, professional, and social achievements. However, the effects of a drug legal or illegal on individual health are determined not only by its pharmacologic properties but also by its availability and social acceptability.
In this respect, legal drugs alcohol and tobacco offer a sobering perspective, ing for the greatest burden of disease associated with drugs 77 not because they are more dangerous than illegal drugs but because their legal status allows for more widespread exposure. As policy shifts toward legalization of marijuana, it is reasonable and probably prudent to hypothesize that its use will increase and that, by extension, so will the of persons for whom there will be negative health consequences.
No potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM. National Center for Biotechnology InformationU. N Engl J Med. Author manuscript; available in PMC Apr Nora D. VolkowM. BalerPh. ComptonM. WeissPh. Author information Copyright and information Disclaimer. Address reprint requests to Dr. Volkow: vog. Copyright notice. The publisher's final edited version of this article is available at N Engl J Med.
See other articles in PMC that cite the published article. Open in a separate window. Figure 1. Glaucoma Early evidence of the benefits of marijuana in patients with glaucoma a disease associated with increased pressure in the eye may be consistent with its ability to effect a transient decrease in intraocular pressure, 5354 but other, standard treatments are currently more effective. Nausea Treatment of the nausea and vomiting associated with chemotherapy was one of the first medical uses of THC and other cannabinoids.
AIDS-associated anorexia and wasting syndrome Reports have indicated that smoked or ingested cannabis improves appetite and le to weight gain and improved mood and quality of life among patients with AIDS.
Chronic pain Marijuana has been used to relieve pain for centuries. Inflammation Cannabinoids e. Multiple sclerosis Nabiximols Sativex, GW Pharmaceuticalsan oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis.
Figure 2. Students in Grade 12, — Panel A shows the inverse correlation between the perception of the risk associated with marijuana use and actual use. Footnotes No potential conflict of interest relevant to this article was reported. References 1. Center for Behavioral Health Statistics and Quality.
National survey on drug use and health. Cannabis use and later life outcomes. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol. Prevalence and correlates of cannabis use in developed and developing countries.
Curr Opin Psychiatry. Early-onset drug use and risk for drug dependence problems. Addict Behav. Dynamic mapping of human cortical development during childhood through early adulthood. Rat models of prenatal and adolescent cannabis exposure. Methods Mol Biol. EMBO J.Thc negative effects
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Health Effects of Marijuana