By Joseph Jaramillo
Increasing interest in the therapeutic and recreational use of cannabis demands greater understanding of the effects of cannabis on the brain. The controversial nature of cannabis in our society obstructs our capacity to have a reasoned conversation about the therapeutic potential of cannabis. This has also impeded research initiatives.
Nevertheless, many states have relaxed regulations of medical and recreational use of cannabis, while the federal government is swinging back toward more restrictive policies. Open policies at the state level have produced data about the hazards of cannabis in specific populations, especially among those at risk for certain mental health disorders.
Growing evidence shows how cannabis may have potentially harmful effects on decision-making and behavior. While cannabis has been shown to assist with pain management and improve overall quality of life for many conditions, it may also cause errors in judgment. Cannabis can cause delays in cognitive information processing, which can lead not only to individual problems, but may get in the way of maintaining relationships. Cannabis has been clearly associated with precipitating the onset of and worsening some illnesses, notably psychiatric conditions.
There is growing interest in understanding the therapeutic and pathological potential of different compounds contained within cannabis, most notably tetrahydrocannabinol (THC) cannabidiol (CBD). Though the importance of the other components of cannabis is increasingly recognized, these two compounds may have significant impact.
Cannabis contains various molecules that bind to receptors in the brain, aptly called cannabinoid receptors. Familiar ligands (which bind to those receptors) include THC and CBD, binding to the CB1 and CB2 receptors with various downstream functions on the brain. The primary neurotransmitter involved in innate (endogenous) cannabinoid activity is anandamide, a unique fatty acid neurotransmitter whose name means joy, bliss, or delight. Only recently has this neurotransmitter system been investigated in greater detail, improving our understanding of therapeutic, recreational, and adverse effects of different cannabinoids, and eventually paving the way for novel synthetic drug development.
Despite well-established evidence that cannabis use can exacerbate serious mental illnesses, a deeper understanding of how cannabis affects different regions of the brain (under different external conditions, e.g. acute vs. chronic use, in the presence of mental health illnesses and comorbid substance use disorder, etc.) is required to ground the debate in knowledge, and to provide solid, reliable scientific findings to pave the way for future research.
Foundational understanding is lacking, and while there is a growing body of research looking at various aspects of cannabis’s effect, as is always the case with an evolving body of research early on, methodology has varied across many small studies, without a clear framework to encourage consistent approaches to investigation. One question of obvious importance is, what are the effects of cannabis on key functional areas of the brain? How do functional and connectivity changes within key anatomic regions (“hubs”, in network theory) spread out to the brain networks in which they are central? How does cannabis use, to the extent we understand its effects, play on specific tasks used to study cognition? What, in general, is the effect of cannabis on brain networks including the default mode, executive control, and salience networks (three key networks in the densely interconnected “rich club” of brain networks)? These and related questions are more important as we come to better understand how the mind/brain gap can be bridged by progress in mapping out the human neural connectome.
The expectation is that activity in different brain areas in users (compared with non-users) will correlate with broad changes across functional brain networks. These changes are reflected in patterns of differential performance on a large group of commonly used psychological research tools that capture different aspects of mental function and human behavior. With this key consideration in mind, a multicenter group of researchers set out to collect and examine all the relevant neuroimaging literature looking at the effect of cannabis on the brain and on behavior and psychology. It’s worthwhile to briefly review the meta-analytic approach used and to discuss what kinds of studies were included and excluded, in order to contextualize and interpret the significant findings. The researchers reviewed a large body of literature and then conducted two preliminary assessments to organize the data. Many of the studies they reviewed utilized fMRI (functional magnetic resonance imaging) and PET scans (positron emission tomography), which are common tools to measure indicators of brain activity and.
First, they divided the studies into groups of either increased or decreased activity in various brain areas among users versus non-users. They then matched up anatomic areas with the functional brain networks. In the second layer of refinement, they used “functional decoding” to identify and categorize different groups of psychological functions measured across the existing literature.
Many cannabis research studies look at a large but varying set of psychological functions to see how, if at all, cannabis changes cognitive and emotional processing. Relevant functions included decision-making, error detection, conflict management, affect regulation, reward and motivational functions, impulse control, executive functions, and memory. Since different studies used different assessments under different conditions, developing a pooled analytic approach is necessary to conduct a comprehensive review and analysis. In some studies, patients reported that cannabis alleviated symptoms of depression, characterized by core experiences of loss of enjoyment, excessive negative emotional states, and lack of motivation. Whereas, it was found that heavier users were at increased risk for worsening depression.
In addition to cannabis potentially priming the brain for an addiction to other chemicals and enhancing experiences, users may also find that they are less interested in regular activities when they are not high, leading to decreased enjoyment and motivation. Simultaneously, others find it produces dysphoria, anxiety, unpleasant confusion, or even paranoia.
These effects are different depending on several cannabis use related factors, such as timing and chronicity of use, as well as type of cannabis and relative chemistry considering the many variations among cannabis species and strains. While this study was not able to distinguish between the effects of THC and CBD, as data was not available on concentrations or ratios of these two key components in cannabis, it is likely that they have different effects on brain function which require further investigation to sort out therapeutic potential from recreational and pathological effects.
This study is a foundational study, setting the stage for ongoing research on the effects of various cannabinoids on the brain and providing important data to understand therapeutic and damaging effects of different cannabinoids. The elegant and painstaking methodology of this study shines a spotlight on how cannabis affects the brain, providing significant data about overall effects on brain networks as well as on cognitive and emotional function.
Questions of interest include additional mapping of brain networks and correlating these findings with existing models of the mind, looking at the effect of different types of cannabis and patterns of use, and investigating the effect of cannabinoids (naturally-occurring, endogenous, and synthetic) for therapeutic purposes in different clinical conditions, recreational use, and potentially for performance enhancement. Finally, by providing a coherent framework for understanding the existing literature inclusive of positive and negative effects of cannabis on the brain, this paper centers cannabis research squarely in the mainstream of scientific study, providing a neutral, de-stigmatized platform allowing a more constructive debate on cannabis to evolve. With the growing discussion of legalization we will come to understand the unanswered questions and where we stand on the future of treatments.
