EDITORIAL

 

Liberalising cannabis legislation in South Africa: Potential public health consequences for adolescents and pregnant women

 

 

There is a global trend towards liberalising cannabis legislation amid recognition that previous restrictions caused social harm and impeded medical research on phytocannabinoids.^[1,2] Liberal legisl ation and attitudes toward cannabis may create opportunities to harness the pharmacological benefits of cannabis for epilepsy,^[3] chronic pain,^[4] nausea and spasticity,^[5] among other medical conditions. Nonetheless, laws that potentially increase access to cannabis could have public health consequences with regard to respiratory health, traffic-related injuries, and the mental health of vulnerable populations.^[6] Rigorous debate about these public health concerns is needed as South Africa (SA) moves towards ratifying the Cannabis for Private Purposes Bill^[7] introduced to Parliament in October 2020. The Bill, which is currently before the Portfolio Committee on Justice and Correctional Services, makes provision for adults to possess, cultivate and process a prescribed quantity of cannabis plants, and to use cannabis, while also explicitly acknowledging the need to protect citizens from potential harms. This prompts questions about who should be protected from cannabis harms. Drawing on recent systematic reviews and expert consensus, we argue that adolescents, pregnant mothers, and fetuses are three groups vulnerable to the harmful effects of cannabis, requiring special consideration as noted in recent Portfolio Committee hearings.

 

Cannabis exposure and adolescent development

The lack of well-designed longitudinal studies assessing the impact of cannabis on adolescent health makes it impossible to conclude that adolescent cannabis use is safe.^[8] If anything, the evidence highlights safety concerns, with regular cannabis use during adolescence associated with persistent functional and structural neurological changes,^[9] and cognitive and emotional deficits.^[10] Adolescents are more vulnerable than adults to the negative effects of cannabidiol and tetrahydrocannabinol, with regular exposure during adolescence associated with more severe and persistent negative outcomes than use during adulthood.^[11,12]

Cannabis use during adolescence causes structural, functional and histological alterations in the frontoparietal, frontolimbic, frontostriatal and cerebellar regions of the brain,^[9] and also affects the endocannabinoid system, which is particularly susceptible to the harmful effects of cannabis as it undergoes profound developmental changes during adolescence.^[10] Prolonged cannabis use during adolescence also disrupts the neuromaturation processes that occur during this period, with synaptic pruning and white matter development particularly affected.^[12] Adolescent cannabis use is also associated with cognitive deficits;^[10] adolescents who use cannabis frequently demonstrate more severe executive dysfunction than their adult counterparts.^[13] Critically, it is not yet clear whether these effects are reversible,^[9] with some evidence suggesting that cannabis-related neurocognitive impairments persist into adulthood, even after prolonged abstinence.^[14,15] Furthermore, craving and disinhibition may be greater among adolescents compared with adults, potentially making adolescents more susceptible to substance use disorders.^[13]

Although it is unclear how adolescent cannabis use affects the onset of schizophrenia, some studies indicate this as an area of concern and a reason to delay the age at which cannabis use is initiated.^'[6] Adolescent cannabis use is, however, associated with an increased risk of psychosis in adulthood^[17] and other psychopathology,^[10] including elevated risk of depression, suicidal ideation and suicidal behaviour.^[18] The harmful effects of adolescent cannabis use on mental health appear to be mediated by genetic and environmental factors, although it is unclear how risk factors interact to cause negative outcomes.^[19] Nonetheless, most of the clinical and preclinical data point to a correlation between adolescent cannabinoid exposure and persistent adverse neuropsychiatric outcomes in adulthood.^[15] It is possible that cannabis is not solely responsible for the observed long-lasting neuropsychiatric effects of adolescent cannabis use; however, cannabis is a significant component of the risk profile.^[15]

 

Consequences of perinatal cannabis exposure

Ethical and methodological problems associated with administering cannabis to pregnant women have resulted in an over-reliance on animal models to make inferences about the harms of in utero cannabis exposure. Furthermore, many women who use cannabis during pregnancy also have poor nutrition and inadequate prenatal care, making it difficult to tease out the effects of cannabis on fetal development from these other confounding factors.^[20] Nonetheless, evidence suggests that cannabis use during pregnancy increases the risk of adverse outcomes for women and their neonates,^[20-22] to the extent that the American College of Obstetricians and Gynaecologists advised physicians to discourage use of cannabis during preconception, pregnancy and lactation.^[23]

Prenatal cannabis exposure is associated with an increased risk of fetal growth retardation and childhood behavioural disturbances.^[24,25] Infants exposed to cannabis in utero tend to have lower birthweights and are more likely to need placement in the neonatal intensive care unit compared with infants without exposure.^[21,25] Cannabis use during pregnancy and breastfeeding alters the developmental trajectory of multiple brain regions and may result in lasting functional consequences,^[25,26] including impaired higher-order executive functioning (i.e. impulse control, visual memory and attention)^[27] and attention deficit hyperactivity disorder during childhood,^[28] which affect academic performance and social adjustment. Furthermore, cannabis interferes with the endocannabinoid system (present from approximately day 16 of gestation), believed to be integral to fetal brain development, which in turn could adversely affect fetal brain growth, including structural and functional neurodevelopment.^[20] These observed neurocognitive and behavioural changes seem to persist throughout life.^[26]

The mechanisms through which in utero cannabis exposure causes neurocognitive and behavioural changes are poorly understood, but it appears that cannabis influences epigenetic regulation, potentially causing persistent fetal genetic changes.^[26] Cannabis may be toxic to human chromosomes,^[20] with chromosomal changes caused by in utero cannabis exposure contributing to the lower fecundity and higher miscarriage rates known to occur among women who use cannabis.^[20] The multidimensional chromosomal and genome toxicity of cannabis may also contribute to congenital anomalies and cancer in children.^[29] These detrimental consequences are exacerbated by additional environmental and chemical insults, including poor nutrition and exposure to other toxic substances such as alcohol.^[26]

 

Conclusion

With regard to cannabis use during adolescence and pregnancy scientific research may not have kept pace with the speed at which cannabis laws are being liberalised. This is not to say that cannabi legalisation should be resisted, but rather that the best availabl evidence suggests that adolescent cannabis use should be activel discouraged and that pregnant women should be advised to avoi cannabis use.^[30] It remains to be seen whether the need for cautioi will be reflected in SA's revised legal frameworks.

Jason Bantjes

Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Cape Town, South Africa; Institute for Life Course Health Research, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa jason.bantjes@mrc.ac.za

Bronwyn Myers

Curtin enAble Institute, Curtin University, Perth, Australia; Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Cape Town, South Africa

Charles Parry

Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Cape Town, South Africa; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

 

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