Cognition

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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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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A systematic review of Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia

A 2019 literature review summarizes the finding on using THC and CBD on patients with dementia. Researchers found that Dronabinol and THC were associated with significant improvements in a range of psychiatric scores. Interestingly, cannabis products showed the most promising results in patients whose symptoms were previously unmanageable or resistant to other treatments.

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Benjamin Caplan, MDA systematic review of Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia
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The Cannabinoid System is a Promising Source of Targets for Treating Pain

A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain ECS

The cannabinoid system provides momentum to develop cannabinoid-based medications to treat inflammatory and neuropathic pain as researchers continue to find promising therapeutic targets. These new targets may lead to the formation of novel pain-relief medications that may serve well to alleviate pain for those suffering from cancer, multiple sclerosis, and fibromyalgia. Cannabis-based pain medicine is also being researched for opioid-sparing effects and effectiveness in reducing the necessary dose of opioids.

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Benjamin Caplan, MDThe Cannabinoid System is a Promising Source of Targets for Treating Pain
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THC Has Potential for Treating Agitation in Alzheimer’s Disease

In a crossover trial of 39 patients with Alzheimer’s disease, treatment with nabilone (a synthetic THC analog) was associated with significant improvement in agitation and, remarkably, cognition. Further studies should examine the effects of both THC and CBD in patients with Alzheimer’s disease because anxiety is common in dementia and may exacerbate agitation. 

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Benjamin Caplan, MDTHC Has Potential for Treating Agitation in Alzheimer’s Disease
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Variations in Genes Influences Cannabis’ Acute Effects on Behavior

CNR1 and FAAH variation and affective states induced by marijuana smoking

A recent study has revealed that variations within cannabinoid receptor 1 (CBR1) and fatty acid amide hydrolase (FAAH) influences cannabis’ acute effects on affect. Variations of CBR1 and FAAH are known to be associated with cannabis dependence. The current study now adds that the variations in genes also affect an individual’s behavior when ingesting cannabis. The results of this study provide useful information for understanding an individual’s motivation for marijuana use, as well as risks and associated behaviors.

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Benjamin Caplan, MDVariations in Genes Influences Cannabis’ Acute Effects on Behavior
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Recently Identified Mechanism of Chronic Stress-Induced Pain

Chronic Stress Is Associated with Pain Precipitation and Elevation in DeltaFosb Expression

Researchers have identified Delta-FosB, an osteosarcoma viral oncogene, as a useful molecular marker of sustained pain. The expression of Delta-FosB is significantly elevated by stress-induced pain, exposing its role in the adaptability of nerves. This study supports theories that Delta-FosB plays an important role in drug addiction, depression, and stress adaptation. The interaction between stress, depression, and pain is something that is not yet well-understood. But, as we learn more about cannabis-based medicine, many of the age-old questions about pain have become much clearer.

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Benjamin Caplan, MDRecently Identified Mechanism of Chronic Stress-Induced Pain
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Cannabinoid Receptors Working with Opioid Receptors

The locus coeruleus is a spot in the human brainstem that is integral to our responses to stress, panic, wakefulness, and sleep-wake transitions. Both the cannabinoid receptors and opioid receptors in the locus coeruleus have a synergistic relationship that, once the medical system begins to incorporate more education about cannabinoids, just might change how physicians prescribe pain medication. The interactions of the two receptor types provide a mechanism that could easily and conveniently improve pain control, provide treatments for addiction, and will likely aid those experiencing symptoms of withdrawal. Research focusing on the treatment of opioid addiction with cannabis is ongoing… but hindered by the legal status of cannabis.

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Benjamin Caplan, MDCannabinoid Receptors Working with Opioid Receptors
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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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