MediCabilis™ 100 CBD Isolate

CBD Isolate of unique Cannabis sativa L (LINNEA 315CSE™) in MCT Oil

MediCabilis™ 100 CBD Isolate is a pharmaceutical grade CBD isolated from a unique cultivar of Cannabis sativa L (LINNEA 315CSE™) standardised to 100mg CBD per mL, in a Medium Chain Triglyceride (MCT) oil base.

Medicine Summary

Name

MediCabilis™ 100 CBD Isolate

Active Ingredients

Cannabidiol (CBD) 100mg/mL

Non-Active ingredients and Carrier

Medium Chain Triglycerides (MCT) sourced from coconut

Method of Administration

The oil should be administered with the enclosed syringe, with the oil placed under the tongue or taken orally.

Accessibility

MediCabilis™ 100 CBD Isolate is available for clinical trial use and for patients via the TGA Approved Prescriber (AP) and Special Access Schemes (SAS). It is not a TGA listed or registered medicine.

Description

Pharmaceutical grade CBD isolated from a unique cultivar of Cannabis sativa L (LINNEA 315CSE™) standardised to 100mg CBD per mL, in a Medium Chain Triglyceride (MCT) oil base.

Overdosage

There is no experience of deliberate overdose with MediCabilis™ 100 CBD Isolate in patients. In the case of overdose, treatment should be symptomatic and supportive.

Poison Schedule of the Medicine

Controlled Drug – Schedule 4

Pharmacology

Mechanism of Action and Pharmacodynamic Effects

The primary action of CBD is via the endogenous endocannabinoid system. The endocannabinoid system contains at least two types of cannabinoid (CB) receptors, CB1 and CB2:

  • CB1 is found mainly in nerve terminals of the CNS where it modulates neurotransmitter release
  • CB2 is found primarily in cells of the immune system, and thought to have pain, immune and inflammatory modulating properties1

Cannabidiol (CBD), the active constituent of MediCabilis™ 100 CBD Isolate, acts as a partial agonist at both CB1 and CB2 receptors and is non-psychotropic.

THC has not been shown to exert psychoactive effect at the negligible amount present in MediCabilis™ 100 CBD Isolate.

Pharmacokinetics

Absorption

The resultant maximum concentrations in the blood following oral administration of MediCabilis™ 100 CBD Isolate might be lower than those obtained by inhaling the same dose of CBD, due to a lower rate of absorption and redistribution into fatty tissues.
Medicinal cannabis has a slow absorption when it’s consumed orally and will take 30 to 90 minutes to reach the bloodstream.
A clinical trial with MediCabilis™ 5% CBD ECs315 (Cannabis sativa extract) in healthy volunteers demonstrated2:

  • CBD reached the blood stream in approximately 30 minutes
  • Mean Tmax for CBD ranged between 2 to 5 hours and did not change with increasing doses
Distribution
  • Cannabidiol is highly lipophilic and can be stored in adipose tissue. This may result in CBD being slowly released at sub-therapeutic levels back into the blood stream, then metabolised and excreted via the urine and faeces.
  • Preferential distribution to fat tissue raises the possibility of accumulation of depot in chronic administration, especially in patients with high levels of body fat.3
Metabolism
  • CBD is metabolised in the liver, and approximately one third of the parent drug and their metabolites are excreted in the urine (the remainder via the faeces). The P450-3A sub-family catalyses the formation of other hydroxylated minor metabolites.
  • The metabolism of CBD is extensive, with more than 33 metabolites identified in urine.
  • The major metabolic route is known to be carboxylation, hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups.
Elimination
  • Elimination half-life of CBD following single dose administration of MediCabilis™ 5% CBD ECs315 in healthy volunteers range from 2 to 9 hours.
  • CBD is expected to remain in the bloodstream for about six hours following a single oral administration.

Clinical Trails

No clinical trial data on MediCabilis™ 100 CBD Isolate is currently available. However, a Phase 1 safety and tolerability clinical trial on MediCabilis™ 5% CBD ECs315 has recently been completed and due for publishing.

Indications

MediCabilis™ 100 CBD Isolate does not have approved indications. Use is at the discretion of the prescribing practitioner based on the individual needs of the patient and on the therapeutic evidence of CBD.

A number of conditions for the use of CBD have been documented and are listed for consideration but are not limited to:

  • Management of epileptic seizures and conditions
  • Chemotherapy-Induced nausea and vomiting (CINV)
  • Inflammatory bowel disease
  • Inflammation related conditions
  • Anxiety
  • Multiple sclerosis (MS)
  • Chronic pain included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain

Safety and Potential Side Effects

Potential Side Effects

The most commonly experienced adverse effects are:

  • drowsiness
  • nausea
  • sedation
  • altered sensory perception

The amount of THC is negligible, hence psychiatric effects are not expected. However, caution is advised for patients with a history of THC adverse reactions, or have a history of psychiatric episodes. Should adverse effects occur the medicine should be adjusted by the prescribing practitioners. Patients should promptly report any exacerbation of psychiatric symptoms such as depression, disorientation, feeling over-excited or losing touch with reality, have difficulty speaking, eating (more or less than usual), or hallucinations.

Precautions

  • Patients who commence MediCabilis™ 100 CBD Isolate should be assessed by the prescribing doctor at least four weeks after treatment commences.
  • Mild or moderate dizziness is commonly reported with the use of Cannabis products. This most frequently occurs in the first few weeks of treatment.
  • The consumption of alcohol is not recommended when patients are treated with medicinal cannabis.
  • Extra precautions are advised in managing any serious conditions, including severe CVD, liver or kidney disease.
  • Other minor cannabinoids including THC may be present in this medicine (less than 0.1 mg/mL). Caution is advised for patients with hyper-sensitivity to THC.
Psychiatric Adverse Events

The amount of THC, a psycho-active cannabinoid, is negligible, hence psychiatric effects are not expected. However, should adverse effects occur the medicine should be adjusted by the prescribing practitioners. Patients should promptly report any exacerbation of psychiatric symptoms such as depression, disorientation, feeling over-excited or losing touch with reality, have difficulty speaking, eating (more or less than usual), or hallucinations.

Genotoxicity

No data specific to MediCabilis™ 100 CBD Isolate is currently available. As data becomes available from the ongoing clinical trial, information will be updated to reflect those findings.

Carcinogenicity

No data specific to MediCabilis™ 100 CBD Isolate is currently available. As data becomes available from the ongoing clinical trial, information will be updated to reflect those findings.

Effects on Fertility

MediCabilis™ 100 CBD Isolate is contraindicated for use in pregnancy. At present there is insufficient evidence to establish safety of MediCabilis™ 100 CBD Isolate in pregnancy.

Paediatric Use

Use in children and adolescents below 18 years of age is at the discretion of the prescribing medical practitioner.

Geriatric Use

No data specific to MediCabilis™ 100 CBD Isolate is currently available. However, cannabis extracts with high CBD and low THC have been shown to be well tolerated and suitable for use in the elderly.4

Interaction With Other Medicines

Cannabidiol (CBD) is metabolised by the cytochrome P450 enzyme system.

In vitro studies have shown that CBD is a potent inhibitor of multiple cytochrome P450 enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4. Consequently, it is likely that it will result in an interactive effect when used in conjunction with other pharmacological agents that are metabolised by these cytochromes, although this is yet to be investigated.5

Concomitant treatment with the CYP3A4 inhibitor ketoconazole produced an increase in Cmax and AUC of CBD 2-fold. Therefore, if concomitant drug treatment with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) is started or stopped during treatment with 1:1% (v/v) CBD, a new dose titration may be required.6

Following treatment with the CYP3A4 inducer rifampicin, reductions in Cmax and AUC CBD (50% and 60% reduction, respectively), were observed.6

Concomitant treatment with the CYP2C19 inhibitor omeprazole resulted in no notable change in any of the pharmacokinetic parameters.6

Based on in vitro data, an inhibition of p-glycoprotein at the intestinal level by CBD cannot be excluded. Therefore, caution is recommended upon concomitant treatment with digoxin and other drugs being substrates for p-glycoprotein.7

Presentation and Storage Conditions

Presentation

MediCabilis™ 100 CBD Isolate is a pale yellow liquid. The medical-grade amber glass bottle with stopper is supplied with a graduated syringe and child-proof, tamper-evident polyethylene cap.

Pack Size

25mL and 50mL

Storage Conditions
  • Store below 25° C.
  • Store upright.
  • Keep away from heat and direct sunlight.
  • Keep out of reach of children.
  • Shake the bottle well before use.
  • Do not refrigerate.

Any unused product or waste material should be returned to the pharmacy which supplied the prescription.

Special Precautions For Disposal

MediCabilis™ 100 CBD Isolate is for oral use only.

Dosage and Administration

MediCabilis™ 100 CBD Isolate is for oral use only.

Adults

Determining the optimal individualised dose of MediCabilis™ 100 CBD Isolate may take some weeks, and side effects from either over- or under-dosing may cause temporary problems. If possible, the selected dosage should be maintained for a period of two weeks unless adverse effects such as fatigue are significant. Dosage reduction may be required in such circumstances.

Titration Period

A titration period may be required to reach the optimal dose. The number and timing of administration will vary between patients.

The optimal dose is the lowest dose that achieves the highest benefit. For more information refer to MediCabilis™ CBD Dosage Guidelines.

Children

No data specific to MediCabilis™ 100 CBD Isolate is currently available. MediCabilis™ 100 CBD Isolate should only be used in children and adolescents below 18 years of age at the discretion of a medical practitioner.

Elderly

No data specific to MediCabilis™ 100 CBD Isolate is currently available. Cannabis extracts low in THC and high in CBD have been shown to be well-tolerated in the elderly.4

Patients With Significant Hepatic Or Renal Impairment

No data specific to MediCabilis™ 100 CBD Isolate is currently available. Phase 1 clinical trial on health volunteers showed no clinically abnormalities reported in vital signs, ECG, physical findings or safety laboratory tests.

However effects in patients with significant hepatic or renal impairment has not been assessed. Effects in such patients may be exaggerated or prolonged. Frequent clinical evaluation and monitoring is recommended if prescribed (see PRECAUTIONS).

Method of Administration

The oil should be administered with the enclosed syringe, with the oil placed under the tongue or taken orally.

Overdosage

There is no experience of deliberate overdose with MediCabilis™ 100 CBD Isolate in patients. In the case of overdose, treatment should be symptomatic and supportive.

For information on the management of overdose, contact the Poison Information Centre on 131 126 (Australia).

Product Information

MediCabilis 100 CBD Isolate

Product Information

MediCabilis™ 100 CBD Isolate

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Patient Information

MediCabilis™ 100 CBD Isolate

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Dosage Guide

MediCabilis™ CBD Isolate

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This information is intended for healthcare professional educational use only.

References

  1. Fine P & Rosenfeld M. The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Med J (2013), Vol 4. I.1.
  2. Phase 1 clinical trial conducted on healthy volunteers with MediCabilis products at Nucleus Network. Bod Australia (2019).
  3. Devinsky, O. (2014). Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 791–802.
  4. Palace Z & Reingold D. Medical Cannabis in the Skilled Nursing Facility: A Novel Approach to Improving Symptom Management and Quality of Life. Journal of the American Medical Directors Association vol.20, 1 (2019): 94-98.
  5. Zhornitsky, S. (2012). Cannabidiol in Human – The Quest for Therapeutic Agents. Pharmaceuticals, 5, 529-552.
  6. Stott C, White L, Wright S, Wilbraham D, Guy G. Springerplus. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. 2013 May 24;2(1):236. doi: 10.1186/2193-1801-2-236. Print 2013 Dec.
  7. Holland ML, Lau DT, Allen JD, Arnold JC. The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids. Br J Pharmacol. 2007 Nov;152(5):815-24. Epub 2007 Oct 1.