MediCabilis™ 5% CBD (LINNEA 315CSE™)

Unique Cannabis sativa L (LINNEA 315CSE™) extract in MCT Oil

MediCabilis™ 5% CBD (LINNEA 315CSE™) is a pharmaceutical grade extract from a unique cultivar of Cannabis sativa L (LINNEA 315CSE™) with a consistent cannabinoid profile, standardised to 50mg CBD per mL and no more than 2mg THC per mL, in a Medium Chain Triglyceride (MCT) oil base.

Product Information

MediCabilis™ 5% CBD

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Patient Information

MediCabilis™ 5% CBD

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Dosage Guide

MediCabilis™ 5% CBD

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MEDICINE SUMMARY

Name:

MediCabilis™ 5% CBD (LINNEA 315CSE™)

Active ingredients:

Cannabis sativa L. extract delivering:

  • Cannabidiol (CBD+CBDA) 50mg/mL
  • Cannabigerol (CBG) ~1.5mg/mL
  • Cannabichromene (CBC) ~2mg/mL
  • Cannabidivarin (CBDV) ~1mg/mL
  • delta-9-tetrahydrocannabinol no more than 2mg/mL

CBD is the predominate cannabinoid with 95% present in it’s decarboxylated form. CBDA is the acidic precursor to CBD.

MediCabilis™ 5% CBD ECs315 contains standardised and consistent phytochemical cannabinoid profile.

Terpenes are naturally present in most plant substances, providing some of the associated taste and aroma.1 They are well tolerated and used widely in a number of applications including as natural food and cosmetic flavours.

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™ 5% CBD (LINNEA 315CSE™) 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

Distinct and standardised full phytochemical Cannabis sativa extract in a Medium Chain Triglyceride (MCT) base. Pharmaceutical grade. LINNEA 315CSE™ is a distinct cultivar of Cannabis sativa L. specifically developed to produce the cannabinoid chemotype expressed in the MediCabilis 5% CBD (LINNEA 315CSE™) extract.

OVERDOSAGE

There is no experience of deliberate overdose with MediCabilis™ 5% CBD (LINNEA 315CSE™) 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).

POISON SCHEDULE OF THE MEDICINE

Controlled Drug – Schedule 8

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), an active constituent of MediCabilis™ 5% CBD (LINNEA 315CSE™) , acts as a partial agonist at both CB1 and CB2 receptors and is non-psychotropic.

THC is a psychotropic substance. It’s presence in MediCabilis 5% CBD (LINNEA 315CSE™) is present at no more than 0.2% (2mg/mL). A phase 1 study has confirmed that 1mL of MediCabilis 5% CBD, providing 2mg THC, does not have a psychotropic action. Higher doses of MediCabilis 5% CBD (LINNEA 315CSE™) will provide higher levels of THC.

PHARMACOKINETICS

Absorption:

A clinical trial with MediCabilis™ 5% CBD (LINNEA 315CSE™) (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:

The resultant maximum concentrations in the blood following oral administration of MediCabilis™ 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.

  • Cannabinoids are 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.6
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 (LINNEA 315CSE™) in healthy volunteers range from 2 to 9 hours (mean half-life 5.8 hours).
  • CBD is expected to remain in the bloodstream for about six hours following a single oral administration.

CLINICAL TRIALS

Clinical trial data on MediCabilis™ 5% CBD (LINNEA 315CSE™) is in development. A Phase 1 safety and tolerability clinical trial on MediCabilis™ 5% CBD (LINNEA 315CSE™) has been completed and due for publishing.

INDICATIONS

MediCabilis™ 5% CBD (LINNEA 315CSE™) 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, and full-spectrum extracts of Cannabis sativa.
A number of conditions for the use of Cannabis sativa are documented and listed for clinical 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 (8% or 8 in 100)
  • nausea (8% or 8 in 100)
  • sedation (8% or 8 in 100)
  • altered sensory perception (8% or 8 in 100)

The amount of THC is less than 0.2%, 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.

CONTRAINDICATIONS

  • Hypersensitivity to cannabinoids or to any of the excipients.
  • Any known or suspected history or family history of schizophrenia, or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
  • Pregnancy.
  • Breast-feeding (in view of the considerable levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants).

PRECAUTIONS

  • Patients who commence MediCabilis™ 5% CBD (LINNEA 315CSE™) 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 are present in this medicine. Caution is advised for patients with hyper-sensitivity to THC.
Psychiatric adverse events

Phase 1 clinical trial indicated no psychiatric adverse effects should be expected with MediCabilis™ 5% CBD ECs315 at 1mL. The amount of THC, a psycho-active cannabinoid, is less than 0.2%, hence psychiatric effects are not expected at 1mL. 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™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™) is currently available. As data becomes available from the ongoing clinical trial, information will be updated to reflect those findings.

Effects on Fertility

MediCabilis™ 5% CBD (LINNEA 315CSE™) is contraindicated for use in pregnancy. At present there is insufficient evidence to establish safety of MediCabilis™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™) 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.7

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.8

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.9 Following treatment with the CYP3A4 inducer rifampicin, reductions in Cmax and AUC CBD (50% and 60% reduction, respectively), were observed.9
Concomitant treatment with the CYP2C19 inhibitor omeprazole resulted in no notable change in any of the pharmacokinetic parameters.9

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.10

Abuse potential

There is low potential for abuse due to the low amount of THC (no more than 0.2%).

PRESENTATION AND STORAGE CONDITIONS

Presentation

MediCabilis™ 5% CBD (LINNEA 315CSE™) is a dark green viscous 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.
  • Special precautions for disposal
  • Any unused product or waste material should be returned to the pharmacy which supplied the prescription.

DOSAGE AND ADMINISTRATION

MediCabilis™ 5% CBD (LINNEA 315CSE™) is for oral use only.

Adults

Determining the optimal individualised dose of MediCabilis™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™) is currently available. MediCabilis™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™) 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 taken orally, by placing under the tongue or into the oral cavity.

OVERDOSAGE

There is no experience of deliberate overdose with MediCabilis™ 5% CBD (LINNEA 315CSE™) 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™ 5% CBD (LINNEA 315CSE™)

Product Information

MediCabilis™ 5% CBD

Download
Patient Information

MediCabilis™ 5% CBD

Download
Dosage Guide

MediCabilis™ 5% CBD

Download

 

This information is intended for healthcare professional educational use only.

References:

  1. Gershenzon J & Dudareva N. The function of terpene natural products in the natural world. (2017) 3. 7, 408-414.
  2. Grof C, Cannabis, from plant to pill. British Journal of Clinical Pharmacology (2018) 84, 2463-2467.
  3. Gertsch J. Anti-inflammatory cannabinoids in diet: towards a better understanding of CB(2) receptor action? Commun Integr Biol (2008) 1:S26–8.
  4. Fine P & Rosenfeld M. The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Med J (2013), Vol 4. I.1.
  5. Phase 1 clinical trial conducted on healthy volunteers with MediCabilis products at Nucleus Network. Bod Australia (2019).
  6. Devinsky, O. (2014). Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 791–802.
  7. 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.
  8. Zhornitsky, S. (2012). Cannabidiol in Human – The Quest for Therapeutic Agents. Pharmaceuticals, 5, 529-552.
  9. Stott C, White L, Wright S, Wilbraham D, Guy G. Springerplus. 2013 May 24;2(1):236. doi: 10.1186/2193-1801-2-236. Print 2013 Dec.
  10. Holland ML, Lau DT, Allen JD, Arnold JC. Br J Pharmacol. 2007 Nov;152(5):815-24. Epub 2007 Oct 1