Cannabis preparations

Chatchada Bodhibukkana, Ph.D.

R&D Institute, GPO
Cannabis sativa L. subsp. indica .
• Glandular trichomes เป็นส่วนที่
ผลิต Cannabinoids และ terpenes

• Glandular trichomes พบได้ทั่วทั้ง

ต้น แต่จะมีปริมาณหนาแน่นที่สุด
บริเวณช่อดอก

• ช่อดอก จึงเป็นส่วนสาคัญที่ให้
สารสาคัญ Cannabinoids
(THC, CBD)
 4 5
2 3
1 Extraction •
•
QC of Extract
Appearance
Identification
•
•
•
Formulation
Capsules
Sublingual drops
Oromucosal spray
•
•
•
•
•
QC of Finished
Product
Appearance
Identification
Content of 9-THC
Content of CBD
Microbial limit tests
QC of Raw Material • Content of 9-THC • Suppositories
• Other parameters
• Solvent extraction • Topicals
• Appearance • Supercritical fluid • Content of CBD depend on dosage
• Identification • Loss on drying • Transdermal patches
extraction (CO2) form
• Foreign material • Short path • Microbial limit tests • Inhalers
• Moisture content distillation
• Microbial limit tests
• Metal limits
• Pesticide limits
 SOLVENT EXTRACTION
• PROS:
SOLVENT
SOLVENT Evaporating solvent • Inexpensive- This method doesn’t
require any fancy machinery.
• Simple
• High yield
• CONS:
• Have to evaporate solvent as much as
possible
• Aware - overheated or overmixed
Solvent/extract and also flammable solvent.
mixture

Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/
CO2 EXTRACTION
• PROS:
• Safe when done by professionals-
CO2 is used in countless food
products and is perfectly safe for
consumption
• Yields high-quality
• CONS:
• Very expensive- setup costs start at
approximately $40,000
• Not suitable for industry scale
production

Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/
Oil Extraction
• Pros:
• Easy- This is by far the easiest
extraction method and is a popular
OIL
home option.
• Cons:
• Low Yields- This method produces low
yields of heavily diluted CBD.
• Aware – toxicity of oils (ex. Naptha)
using in the extraction method

Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/
 D 9-THC D 8-THC

CBN

CBC
CBG

CBD

Chemical structures of compounds isolated from

Cannabis sativa organized via family substructure.
Ref : Husni et.al, 2014
Physical and Chemical properties

Chemical formula C21H30O2 C21H30O2

Molecular weight 314.46 314.46
Solubility in water 0.0126 mg/mL 0.0028 mg/mL
Solubility in ethanol 23.6 mg/mL Soluble (1:1)
log P 6.1 6.93
Physical and Chemical properties

Instability

• Oxidation products derived from fatty acid degradation during the storage
period of macerated oils are critical for overall formulation stability.

• Exposure to light was shown to be the greatest single factors in loss of

cannabinoids especially in solutions.
Pharmacokinetics of Cannabis preparations
• นอกจากข้อมูลด้านเภสัชวิทยา การจัดตั้งสูตรตารับสารสกัดกัญชา (Cannabis oil) ต้องพิจารณาถึง
Physical & chemical properties รวมทั้ง Pharmacokinetic ของสารสกัดเพื่อพัฒนาสูตรตารับที่
เหมาะสม มีคุณภาพ ประสิทธิภาพ ความปลอดภัย และตรงตามความต้องการของผู้ป่วย
• เนื่องจากการการได้รับ Cannabinoids รูปแบบรับประทาน ให้ค่าชีวปริมาณออกฤทธิ์
(bioavailability) ต่า จากการผ่าน First-pass metabolism ดังนั้นเพื่อเพิ่มการนาส่งยาเข้าร่างกาย
จึงมีการพัฒนาสูตรตารับในรูปแบบอื่นในการนาส่งยา เช่น Sublingual, Vaporization of product
and inhalation และ Rectal administration
Cannabis preparations
• Pharmaceutical preparations
• CBD
• THC
• THC/CBD
• Synthetic cannabinoids

• Other preparations
• Food supplements/ Cosmetics
 Pet
products
Cannabis oil
- THC
Cosmetics - CBD
Drugs - THC/CBD
Cannabis
products
Synthetic
cannabinoids
- Nabilone
Supplements - Dronabinol
Foods/ Drinks
Ref : https://bedrocan.com/wp-content/uploads/a-primer-to-medicinal-cannabis_lr.pdf
Approved Drugs
Pharmaceutical preparations (Phytocannabinoids)
EPIDIOLEX ® : Oral solutions
USFDA approve : 2018
รักษาโรคลมชักในผู้ป่วยอายุ 2 ปีขึ้นไป Contains : CBD 100 mg/mL
Dosage : เริ่มให้ที่ 2.5 mg/kg วันละ 2 ครั้ง (5 mg/kg/day) หลังจากได้รับยา
1 สัปดาห์สามาถเพิ่มได้ถึง 5 mg/kg วันละ 2 ครั้ง (10 mg/kg/day)
Indication : seizures associated with Lennox-Gastaut syndrome or
Dravet syndrome ในผู้ป่วยอายุ 2 ปีขึ้นไป
Common side effects : sleepiness, decreased appetite, diarrhea,
increase in liver enzymes, feeling very tired and weak, rash, sleep
problems, and infections.
• In an August 2018 call with investors, GW Pharmaceuticals
revealed the price of Epidiolex would cost roughly $32,500 per
patient, per year.
Pharmaceutical preparations (Phytocannabinoids)
SATIVEX® : Oromucosal spays UK Approve : 2010
รักษาภาวะกล้ามเนื้อหดเกร็ง เนื่องมากจากโรค Each 100 microliter spray contains:
ปลอกประสาทเสื่อมแข็ง (MS) 2.7 mg delta-9-tetrahydrocannabinol (THC) and
2.5 mg cannabidiol (CBD).
Dosage : ค่อยๆ เพิ่มปริมาณสเปรย์ 1 สเปรย์ต่อวัน มากสูงสุดถึง 12 สเปรย์ต่อวัน
Indication : Add-on treatment, for symptom improvement in patients
with moderate to severe spasticity due to multiple sclerosis (MS).
Common side effects : palpitations (1.2%), tooth discolouration (2.1%),
oral mucosal disorder (2.2% )
Pharmaceutical preparations (Synthetic cannabinoids)
CESAMET® : Capsules
USFDA Approve : 1985
รักษาอาการคลื่นไส้อาเจียนจากการใช้เคมีบาบัดใน Contains : 1 mg (2.7 µmol) Nabilone per cap
การรักษามะเร็ง และไม่ตอบสนองต่อยาต้านอาการ
คลื่นไส้อาเจียนตัวอื่น Dosage :
ในผู้ใหญ่รับประมาณครั้งละ 1 หรือ 2 mg วันละ 2 ครั้ง สูงสุดไม่เกิน 6 mg
แบ่งให้วันละ 3 ครั้ง
Indication : for the treatment of the nausea and vomiting associated
with cancer chemotherapy in patients who have failed to respond
adequately to conventional antiemetic treatments
Common side effects : drowsiness, vertigo, dry mouth, euphoria
(feeling “high”), ataxia, headache, and concentration difficulties.
Pharmaceutical preparations (Synthetic cannabinoids)
MARINOL® : Capsules USFDA Approve : 1985
1. การเบื่ออาหาร น้าหนักลดในผู้ป่วยเอดส์ Contains : 2.5 mg, 5 mg, 10 mg Dronabinol per cap
2. รักษาอาการคลื่นไส้อาเจียนจากการใช้เคมี Dosage :
บาบัดในการรักษามะเร็ง ขนาดแนะนาเริ่มให้รับประทานครั้งละ 2.5 mg วันละ 2 ครั้ง ก่อนอาหารกลางวัน
และอาหารเย็น 1 ชั่วโมง
Indication :
1. Anorexia associated with weight loss in patients with AIDS.
2. Nausea and vomiting associated with cancer chemotherapy in patients
who have failed to respond adequately to conventional antiemetic
treatments.
Common side effects : abdominal pain, dizziness,
euphoria, nausea, paranoid reaction, somnolence, thinking abnormal and
vomiting.
Unapproved Drugs
 Cannabis preparations
• Pharmaceutical preparations (Oral Solutions)
Preparations Route Content Indication Remark
THC Medical Oral 25mg/g THC -Pain relief (neuropathy/chronic/ N/A
Cannabis Oils 50mg/g THC caused by the rigidity)
100mg/g THC -Reducing nausea
200mg/g THC -Increase appetite
-Alleviate spastic conditions and
painful spasm

CBD Medical Oral 25mg/g CBD -Inflammatory conditions N/A

Cannabis Oils 50mg/g CBD -Spasms
100mg/g CBD -Helpful in controlling epilepsy
200mg/g CBD seizures for adult and minor patients
-Improve sleep problems
 Cannabis preparations
• Pharmaceutical preparations (Oral Solutions)
Preparations Route Content Advantages Remark

THC:CBD Cannabis Oral 25 mg of THC/g -Patients who suffer from extreme N/A
Oils :25 mg of CBD/g weight loss (Cachexia)
-Pain relief (neuropathy/chronic/
caused by the rigidity)
-Reducing nausea
-Increase appetite
-Alleviate spastic conditions and
painful spasm
 Cannabis preparations
• Pharmaceutical preparations
Preparations Route Content Advantages Remark

Bediol®/Bedrocan Can all be Standardized -Relieve pain and spasms เป็นดอกแห้งกัญชามาตรฐาน

used to make medicinal (cramps)
tea inhaled cannabis flos; -Reduces inflammation
สาหรับใช้รับประทาน หรือ ใส่ใน
through an THC 6.3 % -Reduces the psychological side อุปกรณ์เฉพาะสาหรับ
inhaler CBD 8 % effects inhaler/vaporizer
Vaporizer
 Cannabis preparations
• Pharmaceutical preparations (Inhalers)
Preparations Route Content Advantages Remark
Syqe Inhaler Exo® Thermal- 15.1 mg -Accuracy of dosing, safety, ใช้กัญชามาตรฐานจากบริษัท
(For Hospital metered- Standardized tolerability, efficacy and ease of
Use)/Syqe medical dose inhaler cannabis flos use. Bedrocan แหล่งเดียว
(tMDI) -Use in pain clinics, cancer centers,
intensive care units and other
medical institutions.

The Syqe Inhaler™ Thermal- 100 Optimum balance between แบตเตอรี่สามารถชาร์จได้ โดย
metered- microgram symptom relief and psychoactivity,
dose inhaler cannabis regaining their quality of life.
เฉลี่ยในการชาร์จ 1 ครั้งสามารถ
(tMDI) dosing ใช้งานได้ถึง 1 สัปดาห์
precision *ใช้ความร้อนในการเผาไหม้ที่อุณหภูมิ 190 °C และ
ปลดปล่อยยาออกจากอุปกรณ์
 Cannabis preparations
• Pharmaceutical preparations (Suppositories)
Preparations Route Content Advantages Remark
Cannabis Vaginal Strengths -Decrease in the pain and discomfort N/A
Suppositories ranging from often associated with menstruation
/BioMed Botanicals 25 to 200 mg -The cannabinoids directly impact the
THC. immune system and the nerve
endings of the uterus, cervix, ovaries
and surrounding smooth muscle
tissues

Rectal Cannabis Rectal 2.5−5 mg of -Chemotherapy; people suffer from ยังอยู่ในขั้นตอนการวิจัยและ

Suppositories THC severe nausea and thus it is often
impossible for them to digest พัฒนา ยังไม่มีผลิตภัณฑ์วาง
cannabis edibles จาหน่าย
-Benefit surgical patients who cannot
eat immediately
 Cannabis preparations
• Pharmaceutical preparations (Transdermal patches)
Preparations Route Content Indication Remark

Mary’s Medicinals Transcutaneous Ranging from -THC Patches: Appetite loss, -Avoids first-pass metabolism
Transdermal patch 10-20mg CBD, pain, muscle spasms and improves THC
THC, or CBN -CBD Patches: Inflammation, bioavailability of topical
joint issues, muscle spasms, administration
pain, anxiety
-THC-A Patches: Pain relief -Cannabinoids are highly
without THC-related high hydrophobic, transport across
-CBN Patches: Appetite the aqueous layer of the skin is
suppressant, sleep aid the rate-limiting step in the
diffusion process.
 Advantages & Disadvantages of each dosage form
Dosage form Advantages Disadvantages

Capsules • Easy to use • Not appropriate for unconscious patients

• Preferred by patients, usually tasteless and patients who unable to swallow
• Convenient to carry • Difficult to adjust dose
• Long shelf life • Require time for absorption and distribution
• Loss of drug by first pass effect

Oral solutions • Easier to swallow • Not appropriate for unconscious patients

• Easier to adjust dose and patients who unable to swallow
• Easier to administer to children or • Shorter expiration date
elderly patients • May need flavoring agents to mask bad taste
• Require a measuring device
• Difficult to store
• Loss of drug by first pass effect
 Advantages & Disadvantages of each dosage form

Dosage form Advantages Disadvantages

Sublingual drops/ • Easier to adjust dose • Holding the dose in the mouth is an
Oromucosal spray • Rapid absorption - > faster effect inconvenience
• Avoid first pass effect -> higher • Small dose limit
bioavailability

Suppositories • Useful for patients who can’t take drug • May not be suitable after rectal or anal
orally surgery
• Avoid first pass effect • Some patients dislike suppositories
Topicals • Easy to use • Possibility of local irritation at the site of
• Non invasive application
• High levels of patient satisfaction • Skin’s low permeability limits the number of
• Low risk of systemic adverse events drugs that can be deliver
• Local effect • May not suitable for systemic effect
 Advantages & Disadvantages of each dosage form

Dosage form Advantage Disadvantage

Transdermal • Provides a controlled release of the • Possibility of local irritation at the site of
patches medication application
• Avoid first pass effect • Skin’s low permeability limits the number of
• Prolonged duration of action drugs that can be deliver
- > Reduce frequency of dosing
• Flexibility of terminating drug
administration by simply removing the
patch from the skin
Inhaler • Avoid first pass effect • Irritant effects on airway
• Limitation of medication dose due to airway
symptoms
• Need specific device for administration
 Cannabis preparations
• Other preparations (Food supplements)
Preparations Category Content Benefit Remark
CBD living gel cap Food 25 mg CBD per cap -Antioxidant
supplement -Neuroprotectants

The antioxidant strength of CBD

is significantly greater than that
of either Vitamin C or Vitamin E

SYNERGY: Vanilla Food 3mg of THC and -Antioxidant

Dew Drops supplement 3 mg of CBD per -Neuroprotectants
dropper
 SUPPLEMENTS

25 mg CBD
per cap

300 mg CBD oil in

a 15 ml tincture

5 mg of CBD per
serving

3600 mg of CBD
3mg of THC and 3 mg of CBD per dropper
per 120 ml
120 mg CBD/118 ml
 Cannabis preparations
• Other preparations (Foods/Drinks)
Preparations Category Content Benefit Remark
Fx CBD Lemonade Drink 20 mg CBD per can -Relax
Chill shot (60 ml) -Calming effect

Pot O Coffee Drink 10,50,100 mg CBD -Relax

per cup -Calming effect
 Cannabis preparations
• Other preparations (Foods/Drinks)
Preparations Category Content Benefit Remark
Cannabis infused Drink 80 mg of THC -Enjoy
drink -Relax

Sprig Citrus Soda Drink 45 mg of THC -Enjoy

45 mg of THC -Relax
 DRINKS

20mg CBD per can (60 ml)

infused with 45mg of premium THC oil 45 mg of THC 20mg CBD per can (125 ml)

10,50,100 mg CBD per K-Cup

80 mg of THC 10,50,100 mg THC per K-Cup 10 mg CBD/500 ml 90 mg of active CBD per pack
 Cannabis preparations
• Other preparations (Foods/Drinks)
•
Preparations Category Content Benefit Remark
CBD Living Food CBD 10 mg each -Long-lasting relief
gummies -Non-psychotropic
-Anti-inflammatory without
some of the harsh side effects
like stomach ulcer and
gastrointestinal bleeding

CBD Chocolate Food CBD 60 mg per bar -Long-lasting relief

-Non-psychotropic
-Anti-inflammatory without
some of the harsh side effects
like stomach ulcer and
gastrointestinal bleeding
 Cannabis preparations
• Other preparations (Foods/Drinks)
•
Preparations Category Content Benefit Remark
Birthday Cake Food 200 mg THC per bar -Enjoy
-Relax

PEPPERMINT Food 5 mg THC per mint -Enjoy

RELAXING MINTS -Relax
 FOODS

5 mg THC per mint

200 mg THC per bar CBD InfusHoney
250 mg per pot CBD 60 mg per bar

CBD 120 mg per bar

500 mg THC per bar 10 mg of THC per serving CBD 10 mg each

https://www.green-flower.com/articles/550/cbd-edibles
 Cannabis preparations
• Other preparations (Cosmetics)
Preparations Category Content Benefit Remark
CBD Living soap Cosmetic 60 mg of -Rejuvenate skin
CBD/piece -Promoting cell repair
-Moisturization

CBD Living Lotion Cosmetic 250 mg -Rejuvenate skin

CBD/473 ml -Promoting cell repair
-Moisturization
 Cannabis preparations
• Other preparations (Cosmetics)
•
Preparations Category Content Benefit Remark

SYNERGY Relief: Cosmetic 50 mg of THC -Treats localized pain and

CBD & THC Balm and 50 mg of inflammation
CBD per jar -Promoting blood flow
-After workout soreness
-Assist with neuropathic
conditions
 COSMETICS

50 mg of THC and 50 mg of CBD per jar

250 mg CBD/473 ml

100 mg THC, 100 mg CBD/283 g

60 mg of CBD/piece
PET’S PRODUCTS
References
• A primer to medicinal cannabis; https://bedrocan.com/wp-content/uploads/a-primer-to-medicinal-cannabis_lr.pdf

• The Right Dosage From and the Right Route of Administration: Working With Accuracy
• Drugs, Dose Forms, and Delivery Systems, Chapter 3
• Cannabidiol (CBD) Pre-Review Report, Agenda Item 5.2, World Health Organization, November 2017
• Delta-9-tetrahydrocannibinol, WHO Expert Committee on Drug Dependence Pre-Review, Section 1: Chemistry, 2018
• Pavlovic R., Nenna G., Calvi L., et al. Quality Traits of “Cannabidiol Oils”: Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available
Preparations. Molecules. May 2018
• Fairbairn J., Liebmann J., Rowan MG. The stability of cannabis and its preparations on storage. Journal of Pharmacy and Pharmacology, 1976

• Cannabidiol: https://www.drugbank.ca/drugs/DB09061
• Dronabinol: https://www.drugbank.ca/drugs/DB00470
• FULL PRESCRIBING INFORMATION: EPIDIOLEX® (cannabidiol) oral solution
• PRODUCT MONOGRAPH: SATIVEX®
• PRODUCT MONOGRAPH: CESAMET™(nabilone) Capsules
• FULL PRESCRIBING INFORMATION: MARINOL (dronabinol) capsules

• Medical Cannabis Oils: https://panaxia.co.il/medical-oils/

• Bediol®https://english.cannabisbureau.nl/medicinal-cannabis/types-of-medicinal-cannabis
• Syqe Inhaler Exo®: medical https://www.syqemedical.com/
• https://www.epidiolex.com/
• https://global.cbdliving.com/
• https://www.cbdschool.com/epidiolex-cbd-price/
Thank you