DSM-5

Informing Doctors and Patients on Cannabis Use for Pain

Paper Title: Cannabis and Pain: A Clinical Review

Although results from many bench-scientific and preclinical animal trials support the use of medical cannabis for pain management, there is not yet an equal body of evidence in human clinical trials. However, this is, in part, due to the fact that, despite millennia of accounts supporting the use of cannabis to treat a large number of medical concerns, in the shorter history of cannabis research, the number of controlled, double-blind, placebo studies are limited, and to some points of view, may not even be possible. Additionally, in an era where increasingly more patients request cannabis therapy from their clinicians, health professionals are catastrophically undereducated on the topic. Furthermore, given the status of the modern opioid crisis, there is a growing need for alternative pain management strategies: states with medical marijuana laws experience significantly fewer opioid-related deaths than states lacking them. Additional research could reduce these deaths further and provide viable alternatives for patients seeking pain management when other therapies have failed. 

Below are interesting clippings from this article, points that are either described eloquently or bring a welcome addition to the ongoing discussion:

Benjamin Caplan, MDInforming Doctors and Patients on Cannabis Use for Pain
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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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Cannabidiol Treatment for Parkinson’s Disease

Cannabidiol: a hope to treat non‑motor symptoms of Parkinson’s Disease Patients

Cannabidiol (CBD) has recently been postulated as an ideal drug to address the treatment of non-motor symptoms of Parkinson’s Disease (PD) due to its multifaceted mechanism of action. The plethora of effects of CBD includes anti-inflammatory, neuroprotective, anxiolytic, and antipsychotic actions, which improve non-motor symptoms of PD and lift the quality of life for patients coping with the illness. Further research is recommended to garner support for FDA approval.

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Benjamin Caplan, MDCannabidiol Treatment for Parkinson’s Disease
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Development of Cannabis-Based Treatment for Bipolar Disorder

Bipolar disorder and the endocannabinoid system

A recently published article serves as a call for research to be conducted to discover how cannabis could impact the management of bipolar disorder (BD). Presented in the article is a full review of the advantages and disadvantages of cannabis-based medicine in the treatment of BD and provides insight into possible mechanisms might affect the pathophysiology of the disorder. The insights listed within the article provide the rationale for examining the endocannabinoid system, specifically the cannabinoid receptor 2, with the hopes of finding therapeutic targets for mood control associated with BD.  

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Benjamin Caplan, MDDevelopment of Cannabis-Based Treatment for Bipolar Disorder
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Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

Researchers assessed 817 youth (aged 12 to 21) who previously participated in the National Consortium on Alcohol and Neurodevelopment in Adolescence study. They found that 123 subjects (15.2%) had used cannabis in the past year, and that cannabis use impaired inhibitory control, emotional control, and task planning.

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Benjamin Caplan, MDAdolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use
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Video: Cannabidiol as a suggested candidate for treatment of Autism Spectrum Disorder

This 2018 review summarizes the available data regarding the safety and effectiveness of medical cannabis in young ASD patients. Here’s our video adaptation:

  • Autism spectrum disorder (ASD) defines a group of neurodevelopmental disorders that are frequently associated with general cognitive deficits
    • DSM-5 criteria of ASD include:
      • A. Persistent deficits in social communication and social interaction
      • B. Restricted, repetitive patterns of behavior, interests, or activities
      • C. Symptoms must be present in the early developmental period
      • D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
      • E. These disturbances are not better explained by intellectual disability or global developmental delay
    • ASD is frequently accompanied by co-morbidities:
      • sleep disorders
      • attention-deficit/hyperactivity disorder (ADHD)
      • Psychosis
      • Anxiety
      • mood and cognitive disorders
      • epilepsy
    • Despite it being one of the most severe chronic childhood disorders with relatively high prevalence, morbidity and impact on the society, no effective treatment for the core symptoms of ASD is available yet.
    • There is increasing interest in cannabinoids, especially cannabidiol (CBD), as monotherapy or add-on treatment for the core symptoms and co-morbidities of ASD.
  • CBD Use for Epilepsy
    • 20-30% of people with ASD also suffer from epilepsy
    • Surveys conducted among parents of children suffering from epilepsy suggest improvement following treatment with CBD-enriched cannabis extracts. These results however, do not necessarily apply when it comes to treating adults with epilepsy (Alexander et al., 2009).
    • Still, in a retrospective study that examined the effect of CBD enriched medical cannabis oil on children with intractable epilepsy, the treatment caused a reduction in seizure frequency in 89% of patients (Tzadok et al., 2016).
  • CBD Use in Psychiatry
    • CBD in Psychosis
      • In some cases, psychosis can be a comorbidity of ASD, with the simultaneous onset of schizophrenia at adolescence or early adulthood (Sagar et al., 2013).
      • Ineffective
        • A 2006 study that investigated the influence of CBD as monotherapy in treatment-resistant schizophrenia found that it was ineffective (Zuardi et al., 2006).
      • Effective
        • But a 2018 study showed that, in patients with schizophrenia, adding CBD to ongoing antipsychotic treatment resulted in greater antipsychotic activity and beneficial effects, as compared to placebo add-on (Mcguire et al., 2018).
    • CBD and Anxiety
      • Many ASD patients suffer from anxiety disorders that harm their quality of life (Gu, 2017; Haan et al., 2008; Perrin, 2011).
      • CBD may possess anxiolytic effects both in animals and humans (Bergamaschi et al., 2011).
      • When tested in humans, CBD showed an anxiolytic effect in patients that suffer from social anxiety disorder (SAD), contrary to THC that may induce anxiety (Devinsky et al., 2014).
    • CBD, mood and cognitive disorders
      • It was previously shown that a variety of psychiatric co-morbidities may occur in ASD patients, the most common one being mood disorders (Ghaziddin and Zafar, 2008).
      • Risks of THC
        • THC use may be associated with onset or aggravation of depression, bipolar disorder, mania and psychosis (Rong et al., 2017).
        • THC administration may also result in memory impairment (Ranganathan and Souza, 2006; Rong et al., 2017).
      • Benefits of CBD
        • On the other hand, CBD possesses agonistic activity at the 5-HT1A serotonin receptor and shares similar mechanisms with lithium. These pharmacological properties may indicate its potential role in the treatment of mood disorders (Rong et al., 2017).
        • Therapeutic CBD properties were investigated for cognitive deficits as well. In a preclinical study that tested the effect of CBD on cognition in an Alzheimer’s Disease mouse model (APPxPS1), chronic CBD treatment reversed the cognitive deficits without affecting anxiety-related behaviors (Cheng et al., 2014).
    • CBD and sleep disorders
      • Sleep disorders are highly prevalent among children with ASD.
      • In the general population insomnia is the most common sleep complaint, and treatment with medical cannabis may be effective, especially when the insomnia is associated with pain (Gates et al., 2014).
      • It has been claimed that long term use of cannabis may induce sleep disturbances (Gates et al., 2014). however, a case series indicated that CBD treatment may actually improve the quality of sleep in Parkinson’s disease (Chagas et al., 2014).
    • CBD and ADHD
      • ADHD is one of the most common psychiatric co-morbidities in young ASD patients (Ghaziddin and Zafar, 2008), with comorbidity rates in the range of 40-70% (Antshel et al., 2016).
      • In a pilot randomized placebo-controlled experimental study of a cannabinoid medication (an oral spray containing 1:1 ratio of THC:CBD) in adults who suffer from ADHD, there was no significant improvement in the cognitive performance, but there was a significant improvement in the hyperactivity, impulsivity and inhibition measures after the treatment with the medical cannabis (Cooper et al., 2017).
    • The role of cannabis use for social behavior
      • Risks
        • Some studies show that THC administration may lead as well to a reduction in social interaction in rats, while co-administration of CBD seems to attenuate this effect (Malone et al., 2009).
      • Benefits
        • On the other hand, in a study that tested the influence of marijuana smoking on healthy human volunteers, subjects reported retrospectively that while smoking marijuana they were happier, friendlier and calmer, responded more warmly to others, seemed to have a better understanding of their peers’ state of mind and were less likely to respond angrily or defensively. However, they had a harder time focusing and paying attention to what others said (Galanter et al., 1974).
        • CBD Use for Children
    • The administration of cannabinoids for children and adolescents suffering from ASD is a controversial legal and ethical issue (Khalil, 2012).
      • Risks
        • Those who oppose the use of medical cannabis in pediatrics claim that this treatment might harm young children and adolescents’ brain development.
      • Benefits
        • In the field of pediatric mental illnesses, CBD is sometimes used as a treatment for anxiety disorders. In a case report describing a 10-year-old girl who suffered from PTSD after being sexually abused, it was reported that CBD treatment reduced her anxiety and improved her sleep (Shannon, 2016).
  • Conclusions
    • The use of cannabinoids in general and CBD in particular in the treatment of numerous medical and mental conditions, including ASD, is growing rapidly.
    • There certainly is a big gap in the field and such studies are needed before drawing any conclusions on the potential therapeutic applications of cannabinoids in ASD.
    • Further pre-clinical and clinical studies are needed in order to examine the pros and cons of CBD and other cannabinoids in ASD, before they are established as a treatment for ASD symptoms and co-morbidities.

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Benjamin Caplan, MDVideo: Cannabidiol as a suggested candidate for treatment of Autism Spectrum Disorder
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Cognitive Function in Aging Cocaine Smokers is Marginally Lower than Controls

Cognitive function in aging cocaine smokers

A recently published study looking to expose the functional status of older drug users has found that most of their cognitive abilities are equal to their peers who have never smoked cocaine, except for a marginally lower verbal comprehension. Similar studies should continue in order to determine how chronic drug users will affect or challenge public health systems in the future.

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Benjamin Caplan, MDCognitive Function in Aging Cocaine Smokers is Marginally Lower than Controls
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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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Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

A 2018 study showed that, for patients with schizophrenia, adding CBD to ongoing antipsychotic treatment reduced psychotic activity, as compared to placebo add-on

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Benjamin Caplan, MDCannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial
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Influence of the CB1 cannabinoid receptors & antidepressant effects

Study finds that, for patients already taking antidepressants, activating and/or prohibiting the CB1 receptor in the brain might make those antidepressants more effective.

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Benjamin Caplan, MDInfluence of the CB1 cannabinoid receptors & antidepressant effects
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