A conversation with Brian Coffman, Ph.D., about revisiting cannabis-associated psychosis as a potentially separate disorder from schizophrenia

As cannabis becomes increasingly accessible and socially accepted, questions about its impact on mental health are taking center stage. While most people who use cannabis will not develop a serious psychiatric condition, evidence shows that in a vulnerable subset, heavy or frequent use can trigger psychotic episodes or bring an underlying psychotic disorder like schizophrenia to the surface.

A recent study published by Yale researcher Deepak Cyril D’Souza, M.B.B.S., M.D., in the American Journal of Psychiatry explores the notion that cannabis-associated psychosis and schizophrenia may be biologically different.

Alongside it appears ‘Cannabis and Psychosis: Association, Subtype, or Separate Disorder?’ an editorial by Brian Coffman, Ph.D., director of the Clinical Neurophysiology Research Laboratory at the University of Pittsburgh Medical Center Western Psychiatric Hospital and director of research at the University of Pittsburgh Medical Center Brain Mapping Center.

Coffman recently sat down with Managed Healthcare Executive to discuss his take on the results and what they mean for the future of public health.

This interview has been edited for length and clarity.

MHE: What is cannabis-associated psychosis?

Coffman: Cannabis-associated psychosis is psychosis that can be characterized by ocular hallucinations, delusions or altered perceptions that are either related to or concomitant with cannabis use.

MHE: Are some people more at risk than others? Why or why not?

Coffman: This is a great question, and it's something that I think the field is still struggling with. It seems to be the case that some individuals, and it's not known who these individuals are necessarily, have an increased risk of experiencing psychotic episodes or psychotic-like experiences when using cannabis. There is some data to show that people with a family history of psychotic disorders are at increased risk, but that line of research is still ongoing.

One thing that I hope people take away from the review is that cannabis can lead to these psychotic-like experiences. It can also lead to precipitation of schizophrenia and psychotic disorders, but that psychosis that is related to cannabis is not necessarily the same thing as schizophrenia and may be an independent disorder that we need to more closely characterize.

MHE: What about the results suggests they may be separate?

Coffman: This editorial paper was really discussing results from the D'Souza et al. paper that is in the same issue, where they found some similarities and some neurophysiological differences.

One thing that they found was a similarity in a response called the auditory steady-state response. This is something I study very heavily and something that the field has focused on for quite some time. The auditory steady-state response is a kind of resonant response in auditory cortex to stimuli that are delivered externally.

This auditory steady-state response has long been known to be disrupted in schizophrenia. In the D’Souza paper, they found that there was no difference in this deficit in auditory steady-state response between those with psychosis with and without cannabis exposure because it really highlights a similarity in temporal lobe function in those individuals.

It's a shame that they didn't have a third group of control subjects in that paper, because we can't really say if either one of them in this case was deficient. We just know that they were similar, but the authors also included a somewhat more nuanced measure—the slope of the decay in power spectral density. It's a less well studied excitatory and inhibitory balance.

We have a predominance of low-frequency signals in the brain that oscillate maybe once per second or maybe twice per second, and then we have much lower signals in very fast frequencies that oscillate maybe 50 to 100 times per second.

If we plot out the signal in each of these frequencies, in healthy individuals, we have a very left-sided graph where there are a lot of low frequencies and very few high frequencies.

In people who have a reduced balance of excitation and inhibition, we see an increase in the upper frequencies in what's called the gamma band. These higher frequencies usually indicate excitation in the brain, and the lower frequencies usually indicate inhibition in the brain.

In the D'Souza article, what they found was that in people with psychosis without cannabis exposure, they had some disruption of that balance. In those with cannabis exposure, that was not the case. So, it seems to highlight that cannabis-associated psychosis or cannabis-related psychosis does not have this presentation of reduced excitatory-inhibitory balance, although they do show some disrupted, potentially auditory steady-state response.

MHE: Are cannabis-associated psychosis and schizophrenia currently treated the same way?

Coffman: At least at the outset. Generally, when someone comes into the hospital with a psychotic experience, they're treated with an antipsychotic medication, and that's regardless of what generated that psychotic experience. Antipsychotics do a great job at reducing psychotic experiences, but they don't do a great job at addressing the underlying causes of those psychotic experiences. In many cases, we don't even know what those underlying causes are.

A big focus of my research is to try to identify what's causing these issues. Is it temporal lobe dysfunction? Is it reduced synapses at the level of individual neurons? Rather than treating the dopamine system and trying to dull these things across the board with an antipsychotic, maybe we can target specific aspects of brain function that lead to these problems in people with schizophrenia.

MHE: What are the public health implications of these findings?

Coffman: We're in an interesting time right now with cannabis legalization taking hold in many states. People need to be careful during the adolescent period, mostly because that's a time when development is ongoing, and when people start to use cannabis, generally it is in this adolescent period. Similarly, when people start to develop psychosis, it is generally in this adolescent period.

I think a lot of states are limiting use of recreational marijuana to individuals who are either 18 and over or 21 and over. That may not be enough because people are still developing these neural circuits until the age of 25. The same could probably be said for alcohol use, but alcohol use has a much longer history in our country, and I don't think that would be as easy to regulate at this point.

MHE: How does this editorial fit into the greater body of your own research?

Coffman: My work focuses mostly on auditory neurophysiology in people who have just developed a psychosis disorder. These are people who have come into the hospital with their first psychotic episode within the past year or so, and we characterize their auditory responses in general, but also their ability to modulate those auditory responses with attention and with task involvement. We also look at some ability to focus on different features of the auditory environment and how that can be altered by cognitive control, which is another aspect of schizophrenia and psychotic disorders that seems to be impacted.

People will have a reduced ability to focus, a reduced ability to engage working memory processes in the brain and even a reduced processing speed because they're not as able to respond as quickly when things happen. This leads to a lot of social deficits as well, because if you can't process things as quickly as others, if you can't stay focused and if you can't detect things like prosody and voice as well, then it can lead to some social deficits that are really the most impactful in this population.

We've always done drug testing and looked at medical records to identify cannabis users and cannabis non-users, but since writing this editorial and since this issue has come to the forefront, we've started to more carefully characterize cannabis use in these individuals: the frequency, the type of cannabis they're using and if they think they could quit if they wanted to.