Category Archives: Anxiety

Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects.

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“We examined the effects of essential oil from legal (THC <0.2% w/v) hemp variety on the nervous system in 5 healthy volunteers. GC/EIMS and GC/FID analysis of the EO showed that the main components were myrcene and β-caryophyllene.

The experiment consisted of measuring autonomic nervous system (ANS) parameters; evaluations of the mood state; and electroencephalography (EEG) recording before treatment, during treatment, and after hemp inhalation periods as compared with control conditions. The results revealed decreased diastolic blood pressure, increased heart rate, and significant increased skin temperature.

The subjects described themselves as more energetic, relaxed, and calm.

The analysis EEG showed a significant increase in the mean frequency of alpha (8-13 Hz) and significant decreased mean frequency and relative power of beta 2 (18,5-30 Hz) waves. Moreover, an increased power, relative power, and amplitude of theta (4-8 Hz) and alpha brain waves activities and an increment in the delta wave (0,5-4 Hz) power and relative power was recorded in the posterior region of the brain.

These results suggest that the brain wave activity and ANS are affected by the inhalation of the EO of Cannabis sativa suggesting a neuromodular activity in cases of stress, depression, and anxiety.”

 https://www.ncbi.nlm.nih.gov/pubmed/29576792
https://www.hindawi.com/journals/ecam/2018/1709182/

Reduced levels of the endocannabinoid arachidonylethanolamide (AEA) in hair in patients with borderline personality disorder – a pilot study.

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“Endocannabinoids are involved in depressive and anxious symptoms and might play a role in stress-associated psychiatric disorders.

While alterations in the endogenous cannabinoid system have been repeatedly found in patients with posttraumatic stress disorder (PTSD), this system has been mostly neglected in borderline personality disorder (BPD). However, there is first evidence for elevated serum levels of the endocannabinoids arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol (2-AG) in BPD patients compared to healthy controls and PTSD patients.

In this study, hair endocannabinoids were analyzed, reflecting long-term endocannabinoid concentrations. We assessed AEA concentrations as well as 2-AG and the 2-AG main isomer 1-AG (1-AG/2-AG) in hair in women with BPD (n = 15) and age- and education-matched healthy women (n = 16).

We found significantly reduced log AEA in BPD patients compared to healthy women (p = .03) but no differences in log 1-AG/2-AG concentrations. In addition, there was no association between 1-AG/2-AG and hair cortisol, but we found a non-significant correlation between hair concentrations of AEA and cortisol (p = .06).

Our data indicate altered long-term release of endogenous cannabinoids in women with BPD depending on type of endocannabinoid. AEA has been suggested to modulate the basal activity of the endocannabinoid system and seems to attenuate depressive and anxious symptoms. Thus, chronically reduced AEA might contribute to psychiatric symptoms in BPD.”

https://www.ncbi.nlm.nih.gov/pubmed/29546791

https://www.tandfonline.com/doi/abs/10.1080/10253890.2018.1451837?journalCode=ists20

The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling.

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“Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids.

Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1, CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase – FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95).

After 14 days, CBD injections (30 mg/kg) induced anxiolytic responses in stressed animals in the elevated plus-maze and novelty suppressed feeding tests, that were blocked by pre-treatment with a CB1 (AM251, 0.3 mg/kg) or CB2 (AM630, 0.3 mg/kg), but not by a 5HT1A (WAY100635, 0.05 mg/kg) receptor antagonist. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus. AM251 and AM630 abolished the effects of CBD on spines density. However, AM630 was more effective in attenuating the pro-neurogenic effects of CBD. CBD decreased FAAH and increased p-GSK3β expression in stressed animals, which was also attenuated by AM630.

These results indicate that CBD prevents the behavioral effects caused by CUS probably due to a facilitation of endocannabinoid neurotransmission and consequent CB1/CB2receptors activation, which could recruit intracellular/synaptic proteins involved in neurogenesis and dendritic remodeling.”

https://www.ncbi.nlm.nih.gov/pubmed/29510186

https://www.sciencedirect.com/science/article/pii/S0028390818301023

Learning and Memory is Modulated by Cannabidiol When Administered During Trace Fear-Conditioning.

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“Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD).

Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD.

Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process.

Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29432803

https://www.sciencedirect.com/science/article/pii/S1074742718300224

Chronic High Doses of Cannabinoids Promote Hippocampal Neurogenesis

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“Hippocampal neurogenesis is suppressed following chronic administration of the major drugs of abuse (including opiates, alcohol, nicotine, and cocaine). However, CB1-knockout mice display significantly decreased hippocampal neurogenesis, suggesting that CB1 receptors activated by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis.

Cannabinoids can regulate the proliferation of hippocampal NS/PCs by acting on CB1 receptors. They found that both the synthetic cannabinoid HU210 and the endocannabinoid anandamide profoundly promote embryonic hippocampal NS/PC proliferation. Chronic, but not acute, HU210 significantly increases the number of newborn hippocampal neurons in adult rats by promoting NS/PC proliferation.

A significant increase was observed in the hipoppocampal newborn neurons of mice following twice-daily HU210 injection for 10 days.

This suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic  administration.”

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.” https://www.jci.org/articles/view/25509

http://www.science20.com/science_why_not/blog/chronic_high_doses_cannabinoids_promote_hippocampal_neurogenesis

[Genetic association analyses of the endocannabinoid system on anxious phenotype].

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“Accumulating data confirmed that the endocannabinoid system (ECS) is involved in the regulation of stress response and emotional processes, therefore ECS became an important pharmacological target as a potential anxiolytic.

Our results confirmed earlier positive data on the association between ECS and anxious phenotype. According to our findings ECS plays a significant role in the pathomechanism of anxious disorders by a complex mechanism of genetic interaction with the serotonin transporter gene and childhood traumas.”

https://www.ncbi.nlm.nih.gov/pubmed/29411704

 

Cannabinoid Modulation of the Stressed Hippocampus.

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“Exposure to stressful situations is one of the risk factors for the precipitation of several psychiatric disorders, including Major Depressive Disorder, Posttraumatic Stress Disorder and Schizophrenia.

The hippocampal formation is a forebrain structure highly associated with emotional, learning and memory processes; being particularly vulnerable to stress. Exposure to stressful stimuli leads to neuroplastic changes and imbalance between inhibitory/excitatory networks. These changes have been associated with an impaired hippocampal function.

Endocannabinoids (eCB) are one of the main systems controlling both excitatory and inhibitory neurotransmission, as well as neuroplasticity within the hippocampus.

Cannabinoids receptors are highly expressed in the hippocampus, and several lines of evidence suggest that facilitation of cannabinoid signaling within this brain region prevents stress-induced behavioral changes.

Also, chronic stress modulates hippocampal CB1 receptors expression and endocannabinoid levels.

Moreover, cannabinoids participate in mechanisms related to synaptic plasticity and adult neurogenesis. Here, we discussed the main findings supporting the involvement of hippocampal cannabinoid neurotransmission in stress-induced behavioral and neuroplastic changes.”

https://www.ncbi.nlm.nih.gov/pubmed/29311804

https://www.frontiersin.org/articles/10.3389/fnmol.2017.00411/full

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

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“The cannabinoid system is composed of Gi/o protein-coupled cannabinoid type 1 receptor (CB1) and cannabinoid type 2 (CB2) receptor and endogenous compounds. The CB1 receptor is widely distributed in the central nervous system (CNS) and it is involved in the regulation of common physiological functions. At the neuronal level, the CB1 receptor is mainly placed at GABAergic and glutamatergic axon terminals, where it modulates excitatory and inhibitory synapses. To date, the involvement of CB2 receptor in the regulation of neurotransmission in the CNS has not been clearly shown. The majority of noradrenergic (NA) cells in mammalian tissues are located in the locus coeruleus (LC) while serotonergic (5-HT) cells are mainly distributed in the raphe nuclei including the dorsal raphe nucleus (DRN). In the CNS, NA and 5-HT systems play a crucial role in the control of pain, mood, arousal, sleep-wake cycle, learning/memory, anxiety, and rewarding behaviour. This review summarizes the electrophysiological, neurochemical and behavioural evidences for modulation of the NA/5-HT systems by cannabinoids and the CB1 receptor. Cannabinoids regulate the neuronal activity of NA and 5-HT cells and the release of NA and 5-HT by direct and indirect mechanisms. The interaction between cannabinoid and NA/5-HT systems may underlie several behavioural changes induced by cannabis such as anxiolytic and antidepressant effects or side effects (e.g. disruption of attention). Further research is needed to better understand different aspects of NA and 5-HT systems regulation by cannabinoids, which would be relevant for their use in therapeutics.”

https://www.ncbi.nlm.nih.gov/pubmed/29169951

http://www.sciencedirect.com/science/article/pii/S0024320517306069“

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.

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“Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects.

PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design.

Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray. Tmax following both modes of delivery was 3-3.5 hours postdosing. CBD exhibited about a 1-hour lag in absorption when delivered via PTL101. A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC. Bioavailability of CBD in the 10-mg PTL101 dose was 134% relative to the reference spray.

PTL101 is a pharmaceutical-grade, user-friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.”

https://www.ncbi.nlm.nih.gov/pubmed/29125702

http://onlinelibrary.wiley.com/doi/10.1002/cpdd.408/abstract

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

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“The discovery of endocannabinoid’s role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer’s disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington’s disease, Parkinson’s disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer’s disease and dementia, Huntington’s disease, and Tourette syndrome, and dyskinesia in Parkinson’s disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/29073741

http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2017.15.4.301