Medical Cannabis in Clinical Practice Alexander Samuelsson Lead - - PowerPoint PPT Presentation

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Medical Cannabis in Clinical Practice Alexander Samuelsson Lead - - PowerPoint PPT Presentation

Sep 30, 2023 147 likes •501 views

Medical Cannabis in Clinical Practice Alexander Samuelsson Lead Chemist, Nextleaf Solution Strains and Terpenes- whats all the hype? Molecules, Receptors, and Physiological Effects, Oh My! How the science of cannabis informs medical

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Medical Cannabis in Clinical Practice

Strains and Terpenes- what’s all the hype?

Alexander Samuelsson

Lead Chemist, Nextleaf Solution

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Molecules, Receptors, and Physiological Effects, Oh My!

How the science of cannabis informs medical rationale... …Or how I learned to love biological first principles.

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  • What is the physiological rationale for the felt effects of cannabis?
  • How can we leverage this understanding to better utilize cannabis as a

medicine?

Cannabis, how does it even work?

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But first, some plant science!

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  • Cannabis Anatomy
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Trichome anatomy

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Now, onto some biochemistry!

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Enzymes called "Terpene synthases" are responsible for converting precursors into specific terpene and terpene classes. Terpene construction via condensation IPP + DMAPP + enzyme -> monoterpene 30 terpene synthase genes recently discovered Judith Booth, Jonathan Page, Jörg Bohlmann.

Over 140 terpenes confirmed in Cannabis

Biosynthesis of Cannabinoids and Terpenes

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Biosynthesis of Cannabinoids and Terpenes

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Biosynthesis of Cannabinoids and Terpenes

GPP is essential for cannabigerolic acid Cannabinoids in cannabis would not be possible without terpenes

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Cannabis Compounds and Receptors

Cannabidiol (CBD) Δ9-Tetrahydrocannabinol (THC) Myrcene α-Pinene

Receptors are the physiological base for felt effects from compounds in cannabis

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Terpenes – Floral and Functional

Isoprene Rule: General rule for creating terpenes through condensation of isoprene units (C5H8) Configuration of terpene condensation leads to variety of isomers

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Terpenes – Floral and Functional

α β

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Terpenes – Floral and Functional

Monoterpenes

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Terpenes - Analysis

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Up next, receptors

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Receptor Studies: A Cautionary (Rat)Tail

  • Most receptor studies are carried out in

rat models and knockout transgenic mice then analogized to humans.

  • Not conclusive!
  • Gene studies including cloning of human

receptors and radio labelling studies show some evidence between mouse models and human effects.

  • Some parallels
  • Petrie dish results seldom translate to

successful drugs

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Receptor Modulation

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G Protein Coupled Receptors

  • GPCRs – G-protein coupled receptors are

ubiquitous around the brain and body

  • Cannabinoid receptors make up a small

subsection of GPCR type but make up most of the GPCR density in the brain.

  • GPCR example Beta adrenergic drug target
  • salbutamol in puffers.
  • Beta blockers
  • GPCRs make up 34% of all approved sales

volumes and 180 Billion US annually.

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Known Cannabinoid Receptors

  • CB1 receptors located primarily in the brain, central and

peripheral nervous system.

  • Endogenous: Anandamide and 2-AG
  • Exogenous: D9-THC
  • CB2 receptors are also found in low density on some

neurons but primarily throughout the body, gut, and immune cells.

  • Endogenous: 2-AG
  • Exogenous: CBD, Beta-caryophyllene

(cannabimimetic)

  • “Orphan GPRs GPR18 and GPR55 show ligand-receptor

interactions with cannabinoids and may lead to reclassification and addition of new cannabinoid receptors”

  • CB3, CB4, maybe CB5 (adopted) receptors for future

studies

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Cannabinoid Receptors in Humans

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TRPs Channel Receptors – “Terpene” Receptors

  • TRPV1 and other known TRP receptors show terpene affinity.
  • TRPs modulate calcium channels which play a role in action-potential-induced

neurotransmitter release.

  • Several natural products (e.g. Capsaicin, menthol, gingerol) have been shown to affect

channel gating but exact selective pharmacology has yet to be fully developed and understood.

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TRPs Channel Receptors

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Entourage Effect

  • Both CB-GPRs and TRPs co-expressed on synaptic and presynaptic clefts
  • Anandamide has dual action on TRP and CB receptors
  • Modulate calcium channels, affecting neurotransmitter release/inhibition
  • Basis for the physiological rationale of the “entourage effect”, still a theory but

makes sense

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Strain differences

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Strain differences

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Strain differences

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Strain differences

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Strain differences

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Strain differences

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Parting Thoughts

  • Strains of cannabis impart a variety of effects directly related to the chemical

composition and ratios of terpenes and cannabinoids.

  • Terpenes and Cannabinoids interact with the endocannabinoid system.
  • Ligand-receptor interactions are the source and mechanism for the variety of

effects experienced.

  • Look to literature, be wary of rat models, and keep in mind that biosynthetic

pathways, maps, and our understanding evolve as research progresses.

  • Think of what is happening at the cellular level then leverage known effects.
  • Beware small sample sizes!
  • Medical rationale through receptor-ligand interactions found in studies

− Studies launching with greater frequency

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THANK YOU!

  • Special thank you to the sponsors, CCEN, PURESinse, Strainprint, and

everyone for listening!

  • Happy to answer any questions