The Science Underlying Adolescents' Increased Risk from Cannabis

Timmen Cermak, MD

The onset of puberty introduces a period of rapid neurological development characterized by an explosion of synaptic connections, followed by over a decade of pruning, and an

increase in axonal efficiency through myelinization. The THC in cannabis interferes with these neurodevelopmental processes by over-activating the brain’s endogenous cannabinoid system (ECS).

The ECS is our largest neurotransmitter system. It consists of THC-like neurotransmitters such as anandamide and 2-AG, which are synthesized on demand from postsynaptic cell membrane fatty acids, and cannabinoid receptors (CB1R) that are located presynaptically. The ECS is activated by arrival of a wide variety of neurotransmitters at their postsynaptic receptors. Endocannabinoid neurotransmitters are synthesized in response and then diffuse back across the synaptic space to activate CB1R on the presynaptic neuron. Activation of CB1R produces negative feedback on the presynaptic neuron, decreasing the amount of neurotransmitter released by each axonal firing. This process of tonic negative feedback provides homeostatic regulation of brain chemistry.1

THC activates the brain’s cannabinoid receptors more strongly and longer than anandamide or 2-AG. As a result, CB1R downregulate with the first dose of THC, with CB1R upregulation to normal levels taking sufficient time that too frequent repetition of THC use leads to an accumulation of CB1R downregulation. Two weeks of daily THC downregulates CB1R in rats between 20-60% depending on the brain area.2 MRI demonstrates a 20% reduction in CB1R in the frontal lobes of humans using cannabis regularly that takes a month of abstinence to upregulate to normal levels.3 Chronic use leads to 44% reduction in hippocampal synapses.4 Diffusion Tensor Imaging (DTI) reveals increased anisotropy in the anterior commissure connecting the two hemisphere’s frontal lobes5 as well as in axons within each frontal lobe6, demonstrating disturbances in the flow of intracellular fluid from cell body toward synaptic terminals.

These impacts of THC on frontal lobe structure and function are of special relevance to adolescence since the frontal lobes are the last brain region to fully mature. The earlier cannabis use begins, the more profound the impact. This fact is especially well illustrated by the often misinterpreted Dunedin Study.7 A 25-year longitudinal study of 1037 citizens of Dunedin, New Zealand born in 1972/1973 analyzed the long-term cognitive impacts of cannabis. Neurocognitive testing at age 13 established each individual’s baseline frontal lobe functioning, including overall IQ. The level of cannabis use was evaluated at ages 18, 21, 26, 32 and 38, when neurocognitive testing was repeated. Careful reading of the article reporting this study reveals the following points about reductions in IQ caused by, or associated with, cannabis use: • The more persistently adolescent onset users continue using cannabis during adulthood, the greater is their reduction in IQ at 38. • Those who began cannabis use earliest and continued throughout adulthood lost an average of 8 IQ points, which is sufficient to alter academic success and job opportunities. • Stopping cannabis use did not fully restore neuropsychological functioning among adolescent onset former persistent cannabis users. Impairment was still evident for one year or more after cessation of use. • The only individuals at age 38 who showed a reduction in IQ were those who were using marijuana at least once a week during adolescence. Heavy use during adulthood only did not reduce IQ.

Tests measuring IQ are comprised of an aggregate of several subtests. Analysis of the Dunedin data reveals that impairments in early onset persistent users are detected across five areas: Executive Functioning, Processing Speed, Memory, Perceptual Reasoning, and Verbal Comprehension, with the most robust findings being decreased processing speed and impaired executive functions, confirming previous reports.8,9 More specifically, digit symbol testing reveals reduced processing speed, Wisconsin Card Sort reveals increased perseveration and reduced mental flexibility, and Stroop testing reveals increased impulsivity and difficulty ignoring distractions. Participants in the study also identified informants who “knew them well.” These informants reported significantly more everyday life problems with attention and memory among individuals with the most persistent cannabis dependence. This confirms that cognitive deficits caused by cannabis are of more than academic interest.

Presenting this data is not intended to demonize cannabis, but rather to establish the inconvenient truth that frequent use is riskier for adolescents than for adults. The Dunedin study also documented that individuals with early onset cannabis use are more likely to be persistent users during adulthood. This finding is consistent with data showing that Cannabis Use Disorder (CUD) occurs more frequently and more quickly in early onset users.10 For example, an 11-year-old who starts using cannabis has over a 17% chance of being addicted by age 13. Starting at 12 has over a 16% chance of addiction by age 14. Starting at 16 runs almost a 13% risk of addiction by 18. Waiting until 18 to

start cannabis lowers the risk of addiction by age 20 to about 7%. And waiting until 20 brings the risk of developing addiction within two years down to 3% at age 22. The data clearly establish that early onset of marijuana use increases the rate and speed of addiction.

A complexity needs to be introduced at this point. For decades the mantra within addiction medicine has been that addiction is a lifelong progressive disease. Physicians have watched millions of lives end in death or insanity from alcohol and other drugs. Abstinence from all mind-altering drugs and a program of recovery are generally considered the only safe escape from this inevitable downward spiral. However, detailed analysis of Dunedin data shows this dire view does not fit the facts when it comes to cannabis dependence. This work also illustrates the potential for misusing statistics to support one’s ideology. In the Dunedin study, 28% of those who started using cannabis at age 13 had met the criteria for addiction by 18. By 21 years old 34% had been addicted; and a full 43% had met the criteria for CUD by age 30. This would be astoundingly bad news except for one fact – at 30 years old only 15% of those who started using marijuana at age 13 were still addicted during the previous year.11 Lifetime rates of dependence can obscure current rates. Clearly, a 15% addiction rate at age 30 for those who started using at 13 is not good. It is highly likely that the course of life for these 15% has been significantly impacted, and equally likely that those who no longer meet criteria for CUD nonetheless suffer lingering consequences of reduced academic performance when addicted at earlier school age.12 But, data show that 2/3 of those who developed addiction at some point after starting cannabis use at 13 were no longer addicted at 30. They had stopped or reduced their marijuana use to levels below the criteria for CUD. Similarly, 25% of those who started cannabis at age 15 met criteria for addiction at some point by age 30, but only 9% still used marijuana addictively during the year prior to age 30. The conclusion must be that cannabis addiction is not inevitably a lifelong disorder. In fact, 82% of those who have used cannabis at least 10 times stop use by age 34, the majority merely losing interest in the drug.13

Cognitive development is not the only task of adolescence. Even when early CUD spontaneously remits soon enough to safeguard persistent frontal lobe damage, disruptions in psychological development can continue. Interlocking developmental tasks such as the establishment of a stable sense of identity and values, peer group affiliation, autonomy and separation, and transcendence and meaning are all issues needing preliminary resolution in order to launch into adulthood. Completing each of these tasks can be delayed or distorted by youthful devotion to cannabis use.

Adolescents regularly using cannabis can begin identifying outside traditional adult community norms. While this may contribute to creativity and useful rebellion against unwarranted parental expectations, it may also lead to valuing resistance over accomplishment and opposition to parental values rather than discernment of one’s own. The decision to use cannabis can lead to immediate inclusion in a peer group that demands no more of its members than persistent use. Basing a sense of autonomy on smoking pot does not demand the depth of maturity required to establish a sense of identity that emerges from a deeper awareness of one’s own needs, values and aspirations. And finding meaning in the passive transcendence from routine consciousness offered by cannabis may be interesting in the moment, but ultimately does not usually lead to an accumulation of experience that leads to real world goals. While some overly restrained youth may find cannabis encourages more openness to novel experience and freedom of spirit, this is a lesson that needs to guide one’s life rather than simply be repeated endlessly. In the end, persistent cannabis use is more likely to delay and distort adolescent psychological development than to aid it. Comprehending this fact and using this understanding is made more difficult when frontal lobes are functioning at less than an optimal level.

Timmen Cermak MD is an addiction psychiatrist in Marin, a past-president of the California Society of Addiction Medicine, and author of the new book “From Bud to Brain: A Psychiatrist’s View of Marijuana” (Cambridge University Press).

References

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