Tag Archives: CBD

Cannabidiol: a potential treatment for post Ebola Syndrome?

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“Patients recovered from Ebola virus infection may experience short- and long-term physical, neuropsychological and social sequelae, including arthralgia, musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue, confusion, insomnia, short-term memory impairment, anxiety, depression and anorexia, all lasting from 2 weeks to more than 2 years.

Currently there are no treatments for post Ebola sequelae.

We hypothesize that cannabidiol (CBD) may attenuate some of these post Ebola sequelae, several of which have been postulated to result from inflammation and/or an autoimmune response.

CBD has anti-inflammatory actions in various animal models.

Clinical studies have shown that oral administration of CBD, compared to placebo, significantly reduces anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic for insomnia.

Overall, CBD has a number of pharmacological effects that may significantly improve the mental and somatic health of patients suffering from post Ebola sequelae.

In humans, CBD, at therapeutic doses, does not: 1) elicit dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3) affect gastrointestinal transit; 4) produce significant cognitive or psychomotor impairments. Mild sedation and nausea are the most commonly reported adverse effects associated with CBD.

CBD, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post Ebola sequelae.”

https://www.ncbi.nlm.nih.gov/pubmed/27686726

Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets.

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“To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia).

CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects.

In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits.”

https://www.ncbi.nlm.nih.gov/pubmed/18679164

Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

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“Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100β protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100β concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.”

https://www.ncbi.nlm.nih.gov/pubmed/21654550

Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function.

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“Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature brain following hypoxia-ischemia (HI).

We examined whether CBD neuroprotection is sustained over a prolonged period.

In conclusion, CBD administration after HI injury to newborn rats led to long-lasting neuroprotection, with the overall effect of promoting greater functional rather than histological recovery.

These effects of CBD were not associated with any side effects.

These results emphasize the interest in CBD as a neuroprotective agent for neonatal HI.”

https://www.ncbi.nlm.nih.gov/pubmed/22659086

Neuroprotective Effects of Cannabidiol In Hypoxic Ischemic Insult: The Therapeutic Window In Newborn Mice.

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“A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage.

OBJECTIVE:

to test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage.

RESULTS:

CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction.

CONCLUSION:

CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia.”

https://www.ncbi.nlm.nih.gov/pubmed/27686886

The Effect of Chronic Activation of the Novel Endocannabinoid Receptor GPR18 on Myocardial Function and Blood Pressure in Conscious Rats.

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“While acute activation of the novel endocannabinoid receptor GPR18 causes hypotension, there are no reports on GPR18 expression in the heart or its chronic modulation of cardiovascular function. In this study, after demonstrating GPR18 expression in the heart, we show that chronic (2 weeks) GPR18 activation with its agonist abnormal cannabidiol (abn-cbd; 100 µg/kg/day; i.p) produced hypotension, suppressed the cardiac sympathetic dominance, and improved left ventricular (LV) function (increased the contractility index dp/dtmax, and reduced LV end diastolic pressure, LVEDP) in conscious rats. Ex vivo studies revealed increased: (i) cardiac and plasma adiponectin (ADN) levels; (ii) vascular (aortic) endothelial nitric oxide synthase (eNOS) expression, (iii) vascular and serum nitric oxide (NO) levels; (iv) myocardial and plasma cyclic guanosine monophosphate (cGMP) levels; (v) phosphorylation of myocardial protein kinase B (Akt) and extracellular signal regulated kinase 1/2 (ERK1/2) along with reduced myocardial reactive oxygen species (ROS) in abn-cbd treated rats. These biochemical responses contributed to the hemodynamic responses and were GPR18-mediated because concurrent treatment with the competitive GPR18 antagonist (O-1918) abrogated the abn-cbd evoked hemodynamic and biochemical responses. The current findings present new evidence for a salutary cardiovascular role for GPR18, mediated, at least partly, via elevation in the levels of ADN.”

 https://www.ncbi.nlm.nih.gov/pubmed/27676325

Cannabidiol, among Other Cannabinoid Drugs, Modulates Prepulse Inhibition of Startle in the SHR Animal Model: Implications for Schizophrenia Pharmacotherapy.

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“Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings.”

 https://www.ncbi.nlm.nih.gov/pubmed/27667973

Medical Marijuana: Just the Beginning of a Long, Strange Trip?

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Physical Therapy Journal

“Medical marijuana continues to gain acceptance and become legalized in many states. Various species of the marijuana plant have been cultivated, and this plant can contain up to 100 active compounds known as cannabinoids.

Two cannabinoids seem the most clinically relevant: Δ9-tetrahydrocannabinol (THC), which tends to produce the psychotropic effects commonly associated with marijuana, and cannabidiol (CBD), which may produce therapeutic effects without appreciable psychoactive properties.

Smoking marijuana, or ingesting extracts from the whole plant orally (in baked goods, teas, and so forth), introduces variable amounts of THC, CBD, and other minor cannabinoids into the systemic circulation where they ultimately reach the central and peripheral nervous systems.

Alternatively, products containing THC, CBD, or a combination of both compounds, can also be ingested as oral tablets, or via sprays applied to the oral mucosal membranes. These products may provide a more predictable method for delivering a known amount of specific cannabinoids into the body.

Although there is still a need for randomized controlled clinical trials, preliminary studies have suggested that medical marijuana and related cannabinoids may be beneficial in treating chronic pain, inflammation, spasticity, and other conditions seen commonly in physical therapist practice.

Physical therapists should therefore be aware of the options that are available for patients considering medical marijuana, and be ready to provide information for these patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27660328

Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases.

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“Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients’ seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.”

http://www.ncbi.nlm.nih.gov/pubmed/27655472

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

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“Cannabis sativa, commonly called hemp, has thousands of years-long history of medical use. Cannabis extracts were widely used in Europe and North America for their therapeutic value as sedatives, hypnotics, analgesics, muscle relaxants, and anticonvulsant agents. However, cannabis was removed from British and American Pharmacopoeias in 20th century, partially due to politic bias. Although prohibited, many patients were nevertheless self-medicating to obtain therapeutic benefits from cannabis for various conditions, including AIDS wasting syndrome, multiple sclerosis (MS) and spinal injuries. More recently, a growing interest in the therapeutic effects of cannabis has developed following the isolation of cannabinoids, the principal chemical compounds of cannabis, as well as the discovery of endocannabinoids and their cognate receptors in humans. These advances supported legalisation and wide-spread use of cannabis for therapeutic purposes in many countries.

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009397/