Behavior change

Pre-clinical Evidence for Analgesic Effects of Cannabis Doesn’t Match Human Trial Results

Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings

In Summary:

Pre-clinical animal models of pain provide a wealth of data supporting the pain-relief capabilities of cannabis; however, reproducing this data in human clinical trials has proved difficult. Data from the animal pre-clinical trials point to cannabinoids reducing stress responses and pain-evoked stress, desensitizing pain receptors, and increased pain sensitivity in animals that lack cannabinoid receptors. However, human trials present conflicting results: several studies have shown dose-dependent relationships, and in the current review this was experienced by many participants, wherein lower and medium doses provided pain relief, but higher doses triggered increased sensitivity to pain. Controlled studies may show a lack of impressive pain relief effects, personal reports of pain relief associated with cannabis use are nearly universal in retrospective reports. This suggests that there may be an important effect on well-being or mood, rather merely sensory pain. Furthermore, the relieving effects of cannabis appear to impact men and women differently.

Dr. Caplan and the #MDTake:

Additionally, much of pain relief is subjective, in both sensation, description, and inside the study environment. The description of pain varies from person to person, and researchers may be asking the wrong questions to the right people or the right questions to the wrong people. In fact, a growing perspective is that this mismatch may be more common and more pronounced than previously recognized. The makeup of pain is also quite complicated. For instance, a limb might hurt, but if there is swelling or tenderness nearby, those may amplify the discomfort. How can we take the full picture into account in the form of helpful data points? What of the emotional or psychological impacts of pain? Is it even possible that such things can be fully understood, let alone measured reliably? Assuming that emotional phenomenon or stress/suffering can be conveyed to research scientists, how can we ever hope to compare one person’s experience to another’s? For example, one would imagine that frustration associated with the pain experienced by a venerable world war veteran, who has previously endured tremendous and complex pains and associated psychological trauma may be quite different from someone who has never experienced a particular pain before.

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Benjamin Caplan, MDPre-clinical Evidence for Analgesic Effects of Cannabis Doesn’t Match Human Trial Results
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Many Chronic Pain-Related Cannabis Studies Lack “High-Quality” Evidence

Cannabis-based medicines for chronic neuropathic pain in adults (Review)

In Summary:

In a recent Cochrane meta-analysis of studies investigating the use of medical cannabis for chronic neuropathic pain management, the authors determined that no results were what they could consider “high quality.” All data which related to degrees of pain relief, adverse events, and “Patient Global Impression of Change” were largely of very low or low quality, with some outcomes being of moderate quality. The meta-analysis concluded that no existing evidence backs up the use of cannabis for chronic neuropathic pain; however, the quality of evidence examined highlights the need for more controlled studies.  

Dr. Caplan and the #MDTake:

Depending on the system of organization one prefers, pain can be divided up into different subtypes. For one system, it’s three subtypes: neuropathic, nociceptive, and “other.” For another system, pain can be organized by timing (sharp, acute, chronic, breakthrough), location (bone, soft tissue, nerve, referred, phantom), or by the relative system (emotional, cancer, body.) This review discusses the subtype category of “neuropathic pain” as a means of grouping pain to study. The measures used to assess the pain are as subjective as the categories themselves. Clearly, compounding the two subjective divisions is unlikely to produce “high quality” data, but it is a misleading interpretation to take away that there is no good quality information to glean from the observations this review organizes, and also a misinterpretation to jump to an idea that cannabis is not helpful. Rather, given the statistical tools we currently use, and the subjective systems of understanding pain are not well-matched to translating the effects of cannabis on pain into this type of data.

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Benjamin Caplan, MDMany Chronic Pain-Related Cannabis Studies Lack “High-Quality” Evidence
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Spinal Cord Injury and Severe Traumatic Brain Injury Patients Use Cannabis to Manage Symptoms

Cannabis Use in Individuals with Spinal Cord Injury or Moderate to Severe Traumatic Brain Injury in Colorado

In Summary:

Spinal cord injury patients report that medical cannabis helped them alleviate many symptoms of their injury including spasticity, pain, sleep disruptions, stress, and anxiety. Traumatic brain injury patients list their reason for use as reducing stress/anxiety and improving sleep. Both groups of patients reported recreational use prior to and following injury for a variety of reasons.

Dr. Caplan and the #MDTake:

Healing from traumatic injuries is never solely a matter of local tissue changes. The injured tissues, and the experience of being injured create ripple effects which can disrupt multiple other organ systems, and the entire experience of normalcy. A chemical stress response is one of the most common (and often adaptive) responses to an injury, but the burden of stress, adapting to a new illness, and associated loss of normalcy and sleep can be disastrous to the process of healing. As anxiety and sleeplessness snowball into daily problems themselves, a kernel of injury sometimes amplifies to become a life-altering change.

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Benjamin Caplan, MDSpinal Cord Injury and Severe Traumatic Brain Injury Patients Use Cannabis to Manage Symptoms
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Adolescent Cannabis Use Linked to Sleep Disturbances

Sleep Disturbances, Psychosocial Difficulties and Health Risk Behavior

Summary info:

A Dutch study investigated sleep disturbances in adolescents. Sleep disruption was linked to cannabis use, psychosocial difficulties, health risk behavior, and increased suicidality. Additionally, gender disparity in results suggests that girls may be more susceptible to sleep disturbances than boys , a result consistent with past recognition of some gender discrepancies in cannabis activity. These results highlight the importance of discouraging haphazard cannabis use, during adolescence, and the need for further gender-focused research surrounding sleep habits and cannabis use.

Dr Caplan, CED Foundation, and the #MDTake:

There are a few important issues that converge in this review. Generally, the question of adolescents’ use, (as an alternative way of describing the question of effects on a developing brain.) Also, this paper raises valuable questions about how cannabis may be interacting with sleep hygiene, for better or for worse. Psychosocial impact and risky behaviors are very complex topics to engage, even with a fairly large population sample of (n=16,781.) There are lots of intercorrelated topics assessed, analyzed, and discussed in the review, and it is all-too-easy to want to find causal patterns that are not apparent, again for better or worse, unless one chooses to construe the results or interpretation with causation in mind. Realistically, it is very likely to find overlap in a population of adolescents who have psychosocial difficulties, engage in risky behaviors, have increased risk of suicidality, and consume cannabis. To point to one of the components, arbitrarily, as the primary cause of the others is to unnecessarily and unjustly oversimplify a complex set of circumstances. The essential tenet, different genders seem to react differently with cannabis, is an excellent take-away, and also that we have much more still to learn.

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Benjamin Caplan, MDAdolescent Cannabis Use Linked to Sleep Disturbances
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Hope for Cannabis as a Future Treatment for Tourette’s Syndrome

Single center experience with medical cannabis in Gilles de la Tourette syndrome

A small study on adult Tourette’s patients demonstrated a reduction in tics after treatment with medical cannabis. Treatment with cannabis resulted in a global impression of efficacy score of 3.85 out of 5, signifying an improvement of symptoms. However, many patients reported undesirable effects that resulted in their withdrawal from the trial. Cannabis holds potential for Tourette’s syndrome treatment, however, more work is required to better understand what is causing the positive effects and to flush out reproducible benefits while minimizing the undesirables.

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Benjamin Caplan, MDHope for Cannabis as a Future Treatment for Tourette’s Syndrome
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Reducing Cannabis Use Equally Effective as Abstinence in Treating Cannabis Use Disorder

Reduction in Cannabis Use and Functional Status in Physical Health, Mental Health, and Cognition

In a survey of 111 cannabis use disorder (CUD) patients with abstinent, low use, or heavy use of cannabis, similar benefits were experienced by patients who reduced their use to zero or low use. Both groups exhibited significantly better outcomes than the heavy use group with respect to overall health, appetite, and depression. According to the study, CUD patients “who used cannabis at a low level did not differ from the abstinent individuals in any of the functional outcome measures.” With a relatively small subject population, it is challenging to know if this is applicable to broader audiences, but regardless, It is likely to open up some new treatment option for CUD patients.

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Benjamin Caplan, MDReducing Cannabis Use Equally Effective as Abstinence in Treating Cannabis Use Disorder
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Cannabinoid Receptors Regulating the Function of Opioid Receptors

Constitutive Activity of the Cannabinoid CB1 Receptor Regulates the Function of Co-expressed Mu Opioid Receptors

Summary info:

Cannabinoid receptors have been found to regulate the function of co-expressed mu-opioid receptors. Researchers have found data that indicates the constitutive activity within the cannabinoid system reduced the capacity of expressed mu-opioid receptor functions. This research brings to light the possible benefits of modulating opioid consumption with  cannabis-based medicines. 

Dr Caplan Discussion Points:

One of the interesting discussion points in this paper is a close look at the effects of the CB1 receptor and its capacity to reduce the function of some mu-opioid receptors, through a mechanism different than naloxone. This suggests some appropriate optimism for cannabinoid-based tools in the battle against the worldwide opioid epidemic.

Learn more at http://bit.ly/2wRsbbt 

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Benjamin Caplan, MDCannabinoid Receptors Regulating the Function of Opioid Receptors
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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: 4 major risks of recreational cannabis use

Though cannabis has many medical benefits, using the drug without professional guidance can cause serious harm. Watch this video to learn about 4 major risks associated with recreational cannabis use

Benjamin Caplan, MDVideo: 4 major risks of recreational cannabis use
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