Behavior change

Cannabinoids Further Demonstrate Therapeutic Potential in Interactions with Adrenaline and Serotonin Systems

Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effects

In Summary:

Among many system-wide interactive effects, the noradrenergic and serotonergic hormone/signaling systems are responsible for pain, mood, arousal, wakefulness, learning, anxiety, and feelings of reward. A recent review dives deeper into the interactions between cannabinoids and these two systems: cannabinoids play roles in exciting, inhibiting, and regulating the nerve activity and feedback of both the noradrenergic and serotonergic systems. This data further underscores the therapeutic potential of cannabis for conditions such as depression, chronic pain, and insomnia, all of which are mediated, at least in part, by these systems. Further research may uncover more specific therapies targeted toward the noradrenergic and serotonergic systems and their interactions with cannabinoids.

Dr. Caplan and the #MDTake:

It would be shocking to imagine that, in addition to the usual fruits and vegetables on display at supermarkets, all of a sudden, there was a new category of healthy food. Similarly, the recognition that cannabinoids play a central role in animal physiology is embarrassingly recent. Surveying a sea of illnesses that have become increasingly common, over the last hundred years, before which cannabis was a common household product, also begs the question about a relationship between the circumstances. Might some of the common maladies of modern medicine be attributable to a cannabinoid deficiency syndrome?

A Schematic overview for regulation of NA/LC and 5-HT/DRN cells by the CB1 receptor
Neurochemical Evidence for cannabinoid-induced effects
Electrophysiological evidence for acute effects of cannabinoids on neuronal activity
Neurochemical evidence for cannabinoid-induced effects in the locus coeruleus
Functional evidence fo cannabinoid-induced effects
Electrophysiological evidence for acute effects of cannabinoids

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Benjamin Caplan, MDCannabinoids Further Demonstrate Therapeutic Potential in Interactions with Adrenaline and Serotonin Systems
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Pre- and Post-natal Tobacco and Cannabis Exposure Impacts Children in a Sex-Specific Manner

Pre- and postnatal tobacco and cannabis exposure and child behavior problems: Bidirectional associations, joint effects, and sex differences

Summary Info:

Prenatal maternal cannabis and tobacco use is predictive of behavioral problems among toddlers. Resulting differences from control groups include anxiety, depression, and attention problems. Female children of mom’s consuming substances, in particular, seem to be more susceptible to problems relating to internalization, attention, and sleep. Additionally, the behavioral problems induced by prenatal cannabis and tobacco consumption often lead to further maternal substance consumption, which frequently exacerbates existing behavioral problems. 

Highlights of study of mother's prenatal and postnatal consumption of  cannabis
Highlights of interplay of mother's prenatal and postnatal consumption of  cannabis with children
Highlights of interplay of mother's prenatal and postnatal consumption of  cannabis with toddlers

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Benjamin Caplan, MDPre- and Post-natal Tobacco and Cannabis Exposure Impacts Children in a Sex-Specific Manner
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Veterans Using Cannabis Medicinally More Likely to have PTSD than Recreational Users

Title: Medicinal versus Recreational Cannabis Use among Returning Veterans

In Summary:

A recent study found significant mental and physical health differences between veterans who use cannabis that they label as “medicinal” use versus those who prefer to label their use as “recreational.” Veterans who feel that they are self-medicating with cannabis, in what they believe fits more closely with a “medical” label are five times more likely to suffer from post-traumatic stress disorder (PTSD), nearly four times more likely to suffer from Major Depressive Disorder, and are more likely to experience Insomnia, or trouble sleeping. Furthermore, a majority of veterans medicating with cannabis suffer from conditions that qualify them to receive a medical marijuana registration card. Even so, they tend to refrain from discussing their interest in access with their doctors, out of fear of losing their valuable VA benefits.

Dr. Caplan and the #MDTake:

Over the years, countless veterans have valiantly and courageously dedicated themselves to missions of support for their fellow men, women, and country. In preparation, training, service, battle, leadership, education, and so many other ways, veterans have given back to their culture in a way few others can. The understanding that they may be shunned by their culture for seeking help, related to the suffering they may have experienced while serving their country, is unconscionable. It is shameful that the government and military have not appreciated and supported the easy opportunity to give back to our veterans, and it is long overdue that the culture gives back to those who have given a piece of themselves so that others may share the liberties they have served to uphold.

group differences between medicinal and recreational cannabis users in diagnoses, cannabis-related problems, reasons for using marijuana, and other health-related and substance use outcomes

characteristics of medicinal cannabis users

characteristics of medicinal cannabis users

characteristics of medicinal cannabis users

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Benjamin Caplan, MDVeterans Using Cannabis Medicinally More Likely to have PTSD than Recreational Users
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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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