-1 Cannabidiol or β-Caryophylline

which is doing the work?

When examining the CB2 receptor and it’s natural agonists cannabidiol and
β-caryophylline and their binding affinity at the site, it becomes obvious
quickly that there is a large disparity of binding affinity between the two
substances.
When looking at the data we find both with affinity in the nM range, however in
analysis we find that β-caryophylline has an almost 15x greater affinity at the
site than CBD
β-caryophylline has a Ki of 155 nM (¹)
And we find that CBD has a much higher Ki of 2283 nM (²)

At face value it would look as if β-caryophylline is 14.729 times a stronger

binding agent at the site than CBD. It also seems to have very similar
phamacodynamics (¹),(²) as CBD. Further β-caryophylline is present in all
Cannabis tested for terpenes to date( ³)
and in fact may account for a number of its therapeutic actions.
Both show a dose dependent biphasic response suggesting CBD’s positive
effects may be due to it’s low binding affinity inhibiting receptor activation.
This is confounded by the ubiquitous presence of β-caryophylline in
Cannabis with it’s much higher affinity at the CB2 site
Much more needs to be elucidated regarding the overall relationship of
CBD and β-caryophylline at the CB2 site . Understanding how the highly
targeted and selective binding of
β-caryophylline in the hydrophobic region of the amphipathic receptor
relates and compares to the binding affinity of CBD is important as well as
elucidating the broader non-CB2 properties of CBD.
While CB1 receptor research is relatively confined to true cannabinoids,
the CB2 receptors affinity toward β-caryophylline ,it’s cannabinoidal
phamacodynamics and the complete outlining of how the CB2 system
responds to Cannabis remains unresolved. The importance being placed
upon CBD may in fact belong to β-caryophylline in large part. More
research is needed as to the complete nature of CBD and β-caryophylline
as they relate to Cannabis medicine and their fundamental nature at the
CB2 site.
From the data presented it is highly likely that β-caryophylline is largely
responsible for the anti-inflammatory actions found in non-CBD strains as
well as a host of other therapeutic responses not attributable to THC alone.
This presents the question of is a CBD rich strain actually more effective
than a β-caryophylline rich strain ,and if so, is it due to CB2 binding or
other properties?

1) Beta-caryophyllene is a dietary cannabinoid

Ju¨ rg Gertsch*†, Marco Leonti‡§, Stefan Raduner*§, Ildiko Racz¶, Jian-Zhong Chen,
Xiang-Qun Xie, Karl-Heinz Altmann*,
Meliha Karsak¶, and Andreas Zimmer¶
*Institute of Pharmaceutical Sciences, Department of Chemistry and Applied
Biosciences, Eidgeno¨ ssische Technische Hochschule (ETH) Zurich, 8092 Zu¨ rich,
Switzerland; ‡Dipartimento Farmaco Chimico Tecnologico, University of Cagliari,
01924 Cagliari, Italy; ¶Department of Molecular Psychiatry, University of
Bonn, 53115 Bonn Germany; and Department of Pharmaceutical Sciences, University
of Pittsburgh, Pittsburgh, PA 15260
Edited by L. L. Iversen, University of Oxford, Oxford, United Kingdom, and approved
May 6, 2008 (received for review April 14, 2008))

2)Comparative Receptor Binding Analyses of Cannabinoid

Agonists and Antagonists
BRIAN F. THOMAS, ANNE F. GILLIAM, DAVID F. BURCH, MICHAEL J. ROCHE and HERBERT
H. SELTZMAN
Research Triangle Institute, Research Triangle Park, North Carolina
Accepted for publication December 23, 1997 This paper is available online at
http://www.jpet.org

3)Metabolic fingerprinting of Cannabis sativa L., cannabinoids and

terpenoids
for chemotaxonomic and drug standardization purposes
Justin Thomas Fischedick a,⇑, Arno Hazekamp a, Tjalling Erkelens b, Young Hae Choi
a, Rob Verpoorte a
a Division of Pharmacognosy, Section Metabolomics, Institute of Biology, Leiden
University, Leiden, The Netherlands
b Bedrocan BV, P.O. Box 2009, 9640CA Veendam, The Netherlands