Psychosis

Utilizing Cannabidiol in Psychiatric Disorders

S-adenosyl-L-methionine (SAMe), cannabidiol (CBD), and kratom in
psychiatric disorders: Clinical and mechanistic considerations

In summary

Researchers have recently unveiled the benefits and challenges of utilizing cannabidiol (CBD) in the treatment of psychiatric disorders. CBD has been FDA approved for rare epileptic disorders in the United States and has been recognized for its anxiolytic effects. Dosing CBD can be difficult due to various consumption methods, different products offering ratios of CBD: THC (tetrahydrocannabinol) and terpene contents, all of which cause different effects. Along with anxiolytic effects, the anti-inflammatory effects of CBD have also been well documented, acting through various biological mechanisms. Although THC may not be positively recognized for its psychoactive properties, CBD has been documented by major studies to have anxiolytic and antipsychotic effects with added neuroprotective and anticonvulsant effects. The author concludes that due to the minimal side-effects associated with CBD psychiatrists should seriously consider recommending CBD to patients. 

CBD has fallen into a more of a gray area than THC or cannabis in general as it appears to be widely accepted due to its wide availability yet some overarching associations still think poorly of its use. For example, the National Collegiate Athletic Association (NCAA) explicitly prohibits the use of THC and explains that, while not banned, student-athletes should be hesitant to use CBD products as it increases their risk of testing positive for THC and a healthy athlete should have no reason to utilize CBD anyway. Patients are recommended to seriously discuss their CBD use with a physician and do their research to determine how CBD is received by their places of work or other regulatory bodies they engage in. 

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Benjamin Caplan, MDUtilizing Cannabidiol in Psychiatric Disorders
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Dysregulation of the Endocannabinoid System and Psychosis

Peripheral endocannabinoid system dysregulation in first-episode psychosis

In summary

A recent study has found a pattern of dysregulation within the endocannabinoid system in first-episode psychosis patients. Researchers found that the protein expression of cannabinoid receptor 2 and the protein levels of the main synthesizing and degradation enzymes within first-episode psychosis patients was markedly lower than in controls. This research provides further supports the hypothesis that the dysregulation of the endocannabinoid system is a central factor that contributes to the pathophysiology of psychosis disorders. By determining the exact role of the endocannabinoid system in psychosis disorders researchers will be able to determine novel targets for antipsychotic therapies and possible screen for biomarkers in patients before they develop psychosis symptoms. 

Being able to screen for dysregulation within the endocannabinoid system may serve as a possible biomarker for psychotic disorders but other screening techniques may allow physicians to recommend cannabis more efficiently. Some patients experience feelings of anxiety when consuming a cannabis-based product containing tetrahydrocannabinol (THC), the most abundant psychoactive cannabinoid in cannabis plants. If physicians were able to screen for individuals who would experience negative effects when consuming a product containing THC then they would be able to recommend other products for their patients, ensuring safer cannabis use. 

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Benjamin Caplan, MDDysregulation of the Endocannabinoid System and Psychosis
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The Characterization of Synthetic Cannabinoids Psychoses

Clinical characteristics of synthetic cannabinoidinduced psychotic disorders- a single-center analysis of hospitalized patients

In Summary

A recent clinical study in Russia has documented four clinical variants of cannabis-induced psychoses, as well as the signs to recognize them. The researchers limited their study to males, so it is uncertain if these psychotic disorders can also be seen in women. Patients admitted to the emergency room who claimed to have ingested synthetic cannabinoids or tested positive for synthetic cannabinoids during urinalysis and were then asked to give consent. After all of the participants were confirmed to be suffering from psychoses the researchers separated patients into four distinct groups defined by their characteristics and highlighted predominant symptoms so that others may efficiently identify the specific psychoses when a new patient is identified. The data provides a basis for future diagnostic techniques and management. 

The featured report emphasizes the importance of micro-dosing. The dose of cannabis is not reported in the article but is likely to include patients who overindulged in tetrahydrocannabinol (THC) which can have alarming effects. Microdosing prevents excess consumption by suggesting that patients start low and go slow when self-dosing their cannabis. It is also a good idea to keep a product that features cannabidiol (CBD) which mitigates the psychotic effects of THC. Patients should take care to minimize the amount of cannabis they consume so that any pain or other symptoms are treated but psychoactive effects are minimal.


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Benjamin Caplan, MDThe Characterization of Synthetic Cannabinoids Psychoses
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Natural & Cannabinoid Changes in Dopamine: A key to the psychosis question?

Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats- Effect of an acute dose of WIN55212-2

Brief summary:

A recent study has exposed an age-dependent mechanism within the dopaminergic system that relies on cannabinoid receptor 1 (CB1). Adult and adolescent dopamine levels were examined in the presence of a CB1 agonist and increased levels of extracellular dopamine were found in adolescents. This study reveals the different effects cannabis-based medicine has depended on the age of the patient and warrants future research to ensure cannabis has the desired therapeutic effect on patients.   

Dr Caplan Discussion Points:

This adds a helpful layer of insight to the way an animal model of dopamine changes over time, as well as its interaction with exogenous cannabinoids. This sheds light on the natural evolution of the dopamine control system (irrespective of how it interacts with endocannabinoids), and it also points to how cannabinoids may be involved.

This helps to educate the discussion about how psychosis and cannabis use may interact. There is a long-held understanding that dopamine abnormalities in the specific parts of the brain (mesolimbic and prefrontal brain regions) exist in schizophrenia. More recently, research has also strongly suggested that other neurotransmitters, including glutamate, GABA, acetylcholine, and serotonin are also involved in schizophrenia (and, coincidentally, there is also interaction with these other neurotransmitters from various components of cannabis). Nonetheless, this study simply suggests that, by nature, basal dopamine levels increase during adolescence. Also, the study points out that some cannabinoids boost basal levels too. It seems logical to suggest that excessive dopamine may create a problematic force of additional tipping toward illness, within individuals for whom a congenital predisposition toward illness exists.

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Benjamin Caplan, MDNatural & Cannabinoid Changes in Dopamine: A key to the psychosis question?
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Video: Do-It-Yourself Cannabis Tinctures

One of the terrific realities of modern Cannabis is that it is possible, and often quite simple, to make effective products at home. With suitable education and access to testing facilities, the soil, nutrients, and plant growth can be supported at home, lab-tested for make-up and potency, as well as safety-checked for potential microscopic contaminants, and ultimately, individualized medicine can be created right at home!

Here is a sample instructional for just one way that cannabis tincture can be made at home. There are countless others and hopefully, many that are yet to be discovered!

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Benjamin Caplan, MDVideo: Do-It-Yourself Cannabis Tinctures
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In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

A 2019 study found that patients with early-stage psychotic disorders had lower levels of CB1-R (Cannabinoid Receptor – 1) compared to healthy individuals. These findings suggest that targeting CB1R with cannabis-based products could potentially treat psychotic disorders. Interestingly, reductions in CB1R levels were associated with greater symptom severity and poorer cognitive functioning but only in male patients. More research is needed into the intersections of gender and psychotic disorders.

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Benjamin Caplan, MDIn Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis
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Supplementing Antipsychotics with CBD Enhances Psychotic Symptom Treatment

Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

Most schizophrenia medications function by blocking the action of the dopamine D2 receptor and effectively treat positive psychotic symptoms, such as delusions or hallucinations, but fail to treat negative psychotic symptoms, such as lack of motivation or the lack of an ability to feel pleasure. Anecdotal evidence has pointed toward the potential for CBD to attenuate psychotic symptoms in conjunction with normally prescribed antipsychotics; additionally, CBD is not hypothesized to act on the D2 receptor, suggesting that it may afford unique advantages over anti-psychotics.

Researchers interested in further exploring this conducted the first known placebo-controlled CBD trial among schizophrenia patients. Although results did not suggest a potential for CBD to treat negative psychotic symptoms, in conjunction with antipsychotics, the CBD group experienced marked lower levels of positive psychotic symptoms. Both the placebo and CBD groups experienced equal levels of treatment-induced adverse events, suggesting that CBD is well-tolerated.

These results suggest that CBD may be effective in treating not only schizophrenia but also psychotic symptoms associated with Parkinson’s disease and THC-induced psychosis.

Additional Point: CBD has shown to act in a neuroprotective manner and reduce the psychoactive effects of THC, making it a viable option for patients who have experienced negative side effects with THC.

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Benjamin Caplan, MDSupplementing Antipsychotics with CBD Enhances Psychotic Symptom Treatment
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The Relationship between Cannabis and Schizophrenia

Cannabis and Psychosis: Are We any Closer to Understanding the Relationship?

Despite the constant technological gains in medicine, there is still insufficient information and knowledge about who is at risk of developing cannabis psychosis prior to an individual’s exposure to cannabis. Controlled research is limited due to the legal status of cannabis but the growing number of states legalizing medicinal and recreational use of cannabis will likely provide a naturalistic experiment that will produce a prevention strategy for the condition. Current schizophrenia research is limited to western male populations and an overemphasis on the biological model; future research should extend to a more diverse population and sociocultural factors that may lead to schizophrenia.

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Benjamin Caplan, MDThe Relationship between Cannabis and Schizophrenia
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High-potency cannabis and incident psychosis: correcting the causal assumption

Scientists offer a strong counter-position to the belief that cannabis causes psychosis, pointing out the difference between correlation and causation. They argue that smoke exposure from any source (including cigarettes) could explain the reported link between cannabis and psychosis. 

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Benjamin Caplan, MDHigh-potency cannabis and incident psychosis: correcting the causal assumption
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Video: Cannabis For Symptoms of chronic pain, seizures, and inflammation

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Benjamin Caplan, MDVideo: Cannabis For Symptoms of chronic pain, seizures, and inflammation
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