“Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in healthy populations and in several small studies of synthetic cannabinoid agents but there are currently no studies which have examined the effects of the cannabis plant on anxiety and related disorders. In light of the rapidly shifting landscape regarding the legalization of cannabis for medical and recreational purposes, it is important to highlight the significant disconnect between the scientific literature, public opinion, and related policies. The aim of this article is to provide a comprehensive review of the current cannabis treatment literature, and to identify the potential for cannabis to be used as a therapeutic intervention for anxiety, mood, and related disorders. Searches of five electronic databases were conducted (PubMed, MEDLINE, Web of Science, PsychINFO, and Google Scholar), with the most recent in February 2017. The effects of cannabis on healthy populations and clinical psychiatric samples will be discussed, focusing primarily on anxiety and mood disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28636769 http://onlinelibrary.wiley.com/doi/10.1002/da.22664/abstract
Cannabinoids could make opioids more effective, meaning pain relief with lower doses and reduced risk of dependency
“In animal studies, four times less morphine and ten times less codeine was needed when cannabinoids were given at the same time.
The higher the dose of opioid pain relievers, the more likely it is a patient will experience side effects and complications. With the opioid epidemic becoming a pressing problem, researchers are working to find ways to provide pain relief with less risk. To understand whether therapeutic cannabinoids could be an effective strategy to reduce opioid use, researchers at the University of New South Wales and the Centre for Addiction and Mental Health analysed data from 19 pre-clinical studies and nine clinical trials.
“These studies highlight the potential beneficial effects of combining opioids and cannabinoids””
The cannabinoid system and pain.
“Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.” https://www.ncbi.nlm.nih.gov/pubmed/28625720 http://www.sciencedirect.com/science/article/pii/S002839081730285X]]>
Synaptic functions of endocannabinoid signaling in health and disease.
“Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized “on demand” following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB1) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated. These mechanisms include non-retrograde signaling, signaling via astrocytes, participation in long-term potentiation, and the involvement of mitochondrial CB1. Focusing on paradigmatic brain areas, such as hippocampus, striatum, and neocortex, we review typical and novel signaling mechanisms, and discuss the functional implications in normal brain function and brain diseases. In summary, eCB signaling may lead to different forms of synaptic plasticity through activation of a plethora of mechanisms, which provide further complexity to the functional consequences of eCB signaling.” https://www.ncbi.nlm.nih.gov/pubmed/28625718 http://www.sciencedirect.com/science/article/pii/S0028390817302861]]>
Assessing the role of serotonergic receptors in cannabidiol’s anticonvulsant efficacy.
“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model.
While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.”
https://www.ncbi.nlm.nih.gov/pubmed/28624721
http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext
Assessing the role of serotonergic receptors in cannabidiol's anticonvulsant efficacy.
“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model. While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.” https://www.ncbi.nlm.nih.gov/pubmed/28624721 http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext]]>
Metabolism of the Endocannabinoid Anandamide: Open Questions after 25 Years.
“Cannabis extracts have been used for centuries, but its main active principle ∆9-tetrahydrocannabinol (THC) was identified about 50 years ago. Yet, it is only 25 years ago that the first endogenous ligand of the same receptors engaged by the cannabis agents was discovered. This “endocannabinoid (eCB)” was identified as N-arachidonoylethanolamine (or anandamide (AEA)), and was shown to have several receptors, metabolic enzymes and transporters that altogether drive its biological activity. Here I report on the latest advances about AEA metabolism, with the aim of focusing open questions still awaiting an answer for a deeper understanding of AEA activity, and for translating AEA-based drugs into novel therapeutics for human diseases.”
https://www.ncbi.nlm.nih.gov/pubmed/28611591
Endocannabinoid System in Neurodegenerative Disorders.
“Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid (EC) system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs.” https://www.ncbi.nlm.nih.gov/pubmed/28608560 http://onlinelibrary.wiley.com/doi/10.1111/jnc.14098/abstract]]>
Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.
“Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding.” https://www.ncbi.nlm.nih.gov/pubmed/28617940 http://onlinelibrary.wiley.com/doi/10.1111/epi.13815/abstract]]>
A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study.
“Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans.