Mary's Prime Time Issue 2

MARY’S PRIME TIME
Coverage and Commentary on the Top Cannabis Conferences • Issue 2 • 2018
The Golden Age of Cannabis Research?
Is this the golden age of cannabis research? Around the globe there are countless, ongoing research projects involving
cannabis and its many components, particularly cannabidiol (CBD). A simple search on pubmed.gov (the database of the
U.S. National Library of Medicine) demonstrates the dramatic rise of published research papers pertaining to cannabis in
the 21st Century.
Despite a growing mountain of published data demonstrating the safety and efficacy of cannabis in treating multiple
ailments, the U.S. Federal government demonstrates a mind-boggling obstinacy when it comes to the plant. It refuses to
move cannabis out of Schedule 1, the most prohibitive of all U.S. drug schedules. And the reason is, they will repeat over
and over again, “there is not enough research.” Poppycock!
The accompanying chart, compiled from data at the National
Library of Medicine, demonstrates the explosion of published
cannabis research in the past fifteen years. And with each year
there is also a growing number of cannabis conferences. In
2017 the two crown jewels of cannabis research conferences
convened: ICRS in Montreal and IACM in Cologne. These
two organizations have been presenting cannabis research
for many years. ICRS became officially organized in 1992
but held informal meetings as far back as 1970. IACM first
organized in 2000.
This issue of Mary’s Prime Time is focused on these two
exciting scientific conferences. The ongoing exploration of the
cannabis plant is revealing an amazing assortment of potential therapeutic applications and future generations may indeed
look back on this time as the Golden Age of Cannabis Research.
1600
1200
800
400
0
PubMed Articles on Cannabis or CBD 2001-present
2001 2003 2005 2007 2009 2011 2013 2015 2017*
Search word “cannabis”
Search word “CBD”
Conference Facts and Figures
Sponsor: International Cannabis Research Society (ICRS)
Dates: June 23-26, 2017
Venue: Montreal, Quebec, Canada
Attendees: 350
Meeting Background: The ICRS meets annually at various venues around the globe. The meeting is highly technical
with most presentations focusing on scientific discovery as opposed to clinical application. Mary’s Prime Time is
grateful to Martin A. Lee of Project CBD for granting permission to use his summary of the 2017 ICRS meeting.
Next Meeting: June 30th - July 5th, 2017, Leiden, The Netherlands
Sponsor: International Association for Cannabinoid Medicines (IACM)
Dates: September 29-30, 2017
Venue: Cologne, Germany
Attendees: 348
Meeting Background: The IACM meets every two years with most conferences held in Europe. The focus of IACM
is more clinical than that of the ICRS. The full abstract book from the conference can be found at: https://www.
cannabis-med.org/nis/data/file/abstractbook_2017.pdf
Next Meeting: To be announced

ICRS 2017: A Report from Montreal
by Martin A. Lee
Originally published at Project CBD , July 24, 2017. Gratefully used with permission
During the last week of June, more than 400 scientists
from 25 countries met in Montreal for the 27th annual
symposium of the International Cannabinoid Research
Society (ICRS). Several presentations and posters showcased
new findings about cannabidiol (CBD), the non-euphoric
component of the cannabis plant that is transforming the
medical marijuana landscape. In her Young Investigator
Award Presentation, Saoirse O’Sullivan, associate professor
at the University of Nottingham in the United Kingdom,
discussed the cardiovascular effects of cannabidiol: “CBD
causes both acute and time dependent vasorelaxation of rat
and human arteries … and can improve endothelial function
and vasodilator responses in a rat model of type 2 diabetes.”
Moreover, a single dose of CBD was found to decrease “resting
blood pressure and the blood pressure response to stress.”
Other studies indicate that CBD limits brain damage in animal
models of stroke. “Collectively, these data suggest that CBD
is a compound of interest in the cardiovascular system and in
cardiovascular disorders, which need to be tested in relevant
patient groups,” O’Sullivan concluded.
A poster by Dr. Paula B. Dall’Stella, a neuro-oncologist with
Sirio Libanes Hospital in San Paulo, Brazil, documented the
antitumoral effects of CBD in two patients with Glioblastoma
Multiforme (brain cancer) that were resistant to other therapies.
Mary’s Prime Time
Published periodically by
Mary’s Medicinals
Editor-in-Chief: Alice O’Leary Randall
alice@marysmedicinals.com
Contributor: Justin Kander
Design: Jesica Clark
Editorial Assistance: Eloise Theisen
Special thanks to Project CBD for permission to use Martin
A. Lee’s report on the ICRS meeting.
Published by Mary’s Medicinals, Denver, CO
Copyright (c) 2018 - All rights reserved
MarysMedicinals.com
This publication is solely for educational purposes and is not
intended to substitute for the medical advice of a treating physician.
Medicine and cannabis research is an ever-changing science.
Therefore, the editor, contributors and publisher do not accept
responsibility in the event of negative consequences incurred as a
result of the information presented in Mary’s Prime Time. We do not
claim this information is necessarily accurate by rigid scientific and
regulatory standards applied for medical treatment. No warranty,
expressed or implied, is furnished with respect to the material
contained in this publication. Readers are encouraged to consult
with personal physicians with respect to treatment of any medical
condition.
Before and after MRI scans showed “a marked remission … not
commonly observed in patients only treated with conventional
modalities … that could impact survival.”
Several presentations focused on CBD and treatment-resistant
epilepsy. Dr. Fabricio A. Pamplona, scientific director of
Entourage Phytolab in San Paulo, Brazil, compared the efficacy
of a purified CBD isolate to a whole plant CBD-rich oil extract.
Pamplona found the whole plant extract to be a superior option
with higher potency and fewer adverse side effects than singlemolecule
CBD: “There were more reports of ‘improvement
in seizures frequency’ in CBD-enriched extract compared to
purified CBD,” a result that he attributed to the “additional
compounds available in extracts (other than CBD) that may
interact synergistically.”
Israeli researchers at the Technion Institute in Haifa found
that “not all high CBD extracts have the same anticonvulsant
ability.” The Israelis noted that “the terpenoid content in the
cannabis extracts are important for the anticonvulsant effect.”
(Terpenoids are derived from terpenes, the aromatic botanical
compounds that endow cannabis with a unique smell and
confer specific medicinal effects.) “Not all cannabis extracts will
be useful as a treatment for epilepsy,” the Technion researchers
concluded, adding: “[T]he exact cannabinoid and terpenoid
profiles are needed to evaluate the potential anticonvulsant
properties of a cannabis extract.”
Another poster drew attention to the fact that daily use of CBDrich
cannabis oil extracts may lead to a positive THC finding
in a drug test, a concern for many U.S. patients in so-called
“CBD-only states” that have legalized CBD but not the whole
plant. Unfortunately, this poster resurrected the thoroughly
discredited (and financially motivated) theory that CBD may
convert to THC in the stomach. A more likely explanation
is that any whole cannabis plant extract that includes even a
small amount of THC could generate a positive result from a
drug test. Given the unregulated CBD products that proliferate
online, it’s not surprising that some “CBD” oils contain higher
THC concentrations than advertised.
Other scientists probed CBD’s mechanism of action with
respect to nausea, neuropathic pain, anxiety, and other mood
disorders. Researchers at McGill University in Montreal found
that analgesic effects of acute and chronic CBD treatment are
mediated by the serotonin 5HT1a receptor, but this is not
the case for CBD’s antidepressant effects, which seem to be
regulated via other molecular pathways.
The complex role of the 5HT1a receptor with respect to CBD’s
therapeutic properties was addressed in a poster by Aidan J.
Hampson and his colleagues at the National Institute of Drug
Abuse. It was Hampson’s work, published in 1998, that formed
that basis for the U.S. government’s patent on the antioxidant
and neuroprotectant properties of cannabinoids (both THC
2 ICRS 2017: A Report from
Mary’s Prime Time • Issue 2 • 2018

and CBD). More recently, Hampson has shown that the anxietyrelieving
effect of CBD can be blocked in vivo (in a living animal)
by a 5HT1a antagonist, indicating that this receptor is in part
responsible for mediating the anxiolytic effects of cannabidiol.
Curiously, Hampson’s current data suggests that in addition
to binding directly to 5HT1a, cannabidiol may also act as a
positive allosteric modulator of 5HT1a – meaning that CBD
can alter the functionality of this receptor (and other serotonin
receptor subtypes) in such a way as to enhance its binding
efficiency with the endogenous serotonin neurotransmitter. In
other words, CBD may actually magnify the effect of serotonin,
in addition to directly activating the 5HT1a receptor.
• Chronic cannabis use: Carrie Cutler, assistant professor
at Washington State University, provided a much-needed
rejoinder to scientifically dubious assertions that chronic
cannabis use during adolescence causes brain damage and
significant detrimental effects on cognition and IQ. Her
study found that after controlling for confounding variables
no “significant effects of cannabis use were detected on
… measures of memory or executive functioning” other
than “modest problems with verbal free recall (i.e.,
remembering lists of items) and prospective memory (i.e,
remembering to do things in the future).” A second study
presented by Cutler drew attention to marijuana’s stressreducing
effects: “[C]hronic cannabis use is associated
with a blunted stress response and a reduced reliance on
top-down attentional control that does not cause overall
cognitive performance to suffer.”
• Addiction: Vincenzo Di Marzo, a leading cannabinoid
scientist at the Institute of Biomolecular Chemistry
in Naples, Italy, gave a fascinating presentation on the
cessation of nicotine addiction among cigarette smokers
who suffer a traumatic brain injury. Di Marzo identified
an endogenous lipid molecule, N-oleoyol-glycine (OlGly),
which activates a receptor on the membrane of the
Scientists at the University of Louisville School of Medicine in
Kentucky have identified two new molecular targets of CBD
– the receptors designated “GPR3” and “GPR6.” (GPR refers
to G-coupled protein receptor, the family of receptors that
includes cannabinoid, opioid, and several serotonin receptor
subtypes.) GPR3 and GPR6 are both known as “orphan
receptors” because the principal endogenous compounds that
bind to these receptors have yet to be identified.
Some of the potential therapeutic effects of CBD for
Alzheimer’s disease, Parkinson’s disease and schizophrenia may
be mediated by GPR3 and GPR6.
Amyloid beta plaque and tau protein tangles in the brain are
hallmarks of Alzheimer’s dementia. Tim Karl from the Western
Sydney University School of Medicine in Australia elaborated
on CBD’s therapeutic potential for this neurodegenerative
brain disease: “The phytocannabinoid cannabidiol possesses
antioxidant, anti-inflammatory and neuroprotective properties
and prevents amyloid beta-induced neuroinflammation, and
tau hyperphosphorylation in vitro. CBD also reverses cognitive
deficits of pharmacological amyloid beta models. Thus, CBD
may offer therapeutic value for Alzheimer’s disease.”
Another receptor, known as GPR55, is inhibited by CBD.
This is significant because preclinical research has linked
GPR55 activation to several aberrant conditions, including
colon cancer and Dravet Syndrome, a severe seizure disorder.
By functioning as a GPR55 “antagonist,” CBD may confer a
tumor-suppressing and anti-epileptic effect, although clinical
studies have yet to confirm whether this mechanism of action
is applicable to humans as well as animals.
At the 2017 ICRS conference, numerous presentations focused
on other areas of cannabinoid science that do not involve
CBD but are nonetheless relevant for cannabis clinicians and
patients. Some highlights:
Martin A. Lee
cell’s nucleus, thereby reducing the rewarding effects of
nicotine and nicotine-dependence in mice. In a separate
study of morphine withdrawal, Di Marzo and a team of
international researchers concluded: “Oleoyl Glycine is a
newly discovered endogenous cannabinoid-like compound
that may have therapeutic potential in the treatment of
addiction.”
• Pain relief: Temple University scientists found that
“cannabinoids used in combination with opioids have the
potential to reduce the dose of opioids needed for analgesia.”
Jenny L. Wiley, a scientist with RTI International in
North Carolina, and her colleagues at Washington State
University reported encouraging results regarding the use
of THC as a prophylactic treatment for chemotherapyinduced
peripheral neuropathy. “Preliminary data suggest
that THC administered chronically during the course
of paclitaxel treatment decreases the development of
mechanical allodynia [heightened sensitivity to pain] in
both male and female rats.”
• Sleep: Gwen Wurm at the University of Miami reported
that medical cannabis use is associated with a decrease
in the use of prescription and over-the-counter sleep
medications. Moreover, according Wurm’s poster, “There
is a strong relationship between use of medical cannabis
for sleep and for pain.”
Mary’s Prime Time • Issue 2 • 2018
ICRS 2017: A Report from
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• The CB2 receptor: Tel Aviv University scientist Bitya
Raphael identified an endogenous hormone H4(99-
103) that activates the cannabinoid CB2 receptor, which
regulates immune function, metabolic processes and the
peripheral nervous system. This is the first study showing
that an endogenous circulating peptide signals via the CB2
receptor. A poster presented by Makenzie Fulmer at East
Tennessee State University described how CB2 receptor
dysfunction increases plaque calcification in a mouse
model of atherosclerosis.
There were many other significant presentations during the
four-day ICRS conference in Montreal that warrant mention –
too many to adequately address in this summary. Project CBD
looks forward to further developments next year when the ICRS
convenes again at Leiden University in the Netherlands.
IACM 2017: A Report from Cologne
General Session Reporting by Alice O’Leary Randall
Cannabis-based medicines: an introductory overview
Dr. Donald Abrams summarized the recent findings of
the U.S. Committee on the Health Effects of Marijuana:
An Evidence Review and Research Agenda. The 16-member
committee was charged with “conducting a comprehensive
review of the current evidence regarding the health effects of
using cannabis and cannabis derived products.” The report was
commissioned by the
Health and Medicine
Division (Formerly the
Institute of Medicine
[IOM]) of the National
Academies of Sciences,
Highlights from IACM Meeting
Engineering and
Medicine. The IOM is
no stranger to reviewing
cannabis literature
having done so in 1982
and 1999. So it has to
be said that this report,
completed in rather
record breaking time (it
first convened in March
2016 and released its
report less than one
year later in January 2017), does not cover any new ground.
It did exhaustively review the literature, retrieving 24,000
abstracts initially but reducing the number actually reviewed
to 10,700. From that number it arrived at nearly 100 research
conclusions related to cannabis or cannabinoid use.
Of course the Committee called for more research, proposing
a “national cannabis research agenda” that is funded by public
agencies, philanthropic and professional associations, private
companies, and clinical and public health research groups”.
This is the Committee’s #1 recommendation followed by
2) improve research quality, 3) a rather ominous suggestion
to “improve surveillance capacity,” and 4) “address research
barriers” which, amazingly, does not address re-scheduling.
Instead it calls for creation of another committee that can
“fully characterize the impacts of regulatory barriers to cannabis
research.” Quite an astonishing bit of side-stepping since it is
patently obvious to all that the primary impediment to research
is the current scheduling.
The Committee concluded there is conclusive or substantial
evidence for effective cannabis or cannabinoid treatment in
the treatment of chronic pain, nausea and vomiting associated
with chemotherapy treatments, and improving spasticity
associated with multiple sclerosis. It gave a rating of “moderate”
evidence for use of cannabis in treating sleep disturbances
associated with obstructive sleep apnea syndrome, fibromyalgia,
chronic pain, and MS. There is limited evidence for increasing
appetite and decreasing
weight loss for HIV/
AIDS patients,
• Cognitive impairment in “old” mice was reversed by ultra-low doses of
delta-9 THC. Given just 0.002 mg/kg of THC the mice performed
significantly better in a series of standard tests. (See Sarne, page 9)
• The Syqe-Exo is a cannabinoid delivery device that resembles an
Advair inhaler. The manufacturers presented data that demonstrated
ease of use and efficient dosing of cannabis while the the patient was
hospitalized. (See Eisenberg, page 9)
• The first large-scale epidemiological studies of cancer patients and aged
populations, both conducted in Israel, demonstrate patient satisfaction
with medical cannabis as well as demonstrable improvement in
symptoms. (See Schleider and Abuhasira, page 8)
Tourette syndrome,
anxiety, or PTSD. And,
in a confusing bit of
jargon, the Committee
stated there was
limited evidence that
cannabis is ineffective
for dementia, improving
intraocular
pressure associated
with glaucoma, and
depressive symptoms
associated with conditions
such as chronic
pain.
The complete report is available in hard copy or Kindle version.
The formal title of the report is The Health Effects of Cannabis and
Cannabinoids: The Current State of Evidence and Recommendations
for Research. A free copy can be downloaded from the National
Academy website (https://www.nap.edu/catalog/24625/thehealth-effects-of-cannabis-and-cannabinoids-the-current-state).
It is also available in hard copy or Kindle version.
Evaluating the impact of cannabis use in the human
laboratory and via patient registry surveys
Ryan Vandry and his colleagues in Maryland, New York, and
North Carolina have been looking at administration routes,
comparing oral, smoked, and vaporized cannabis products.
While it may seem that these issues have been well addressed
in previous NIDA-sanctioned research the group did include
vaporization which scored the best in terms peak drug effects
4 IACM 2017: A Report from
Mary’s Prime Time • Issue 2 • 2018

suggesting that vaping may be the more efficient method
of cannabis delivery. The researchers also noted that “blood
cannabinoids were better biomarkers of acute drug effects than
oral fluid cannabinoids.” The team was unable, however, to
correlate either marker with performance on cognitive task.
Of more interest to the average cannabis patient was Vandry’s
brief discussion of a collaborative project between Johns
Hopkins University School of Medicine and the Colorado
based Realm of Caring to gather epidemiological data as to
how individuals are using cannabis medically. The team has an
online survey that participants complete every three months.
At present the database consists of almost 1,000 individuals
(500 cannabis users and nearly 400 non cannabis users for
a baseline). All are asked about their medical condition and
cannabis users are asked about route of administration and
strains of cannabis, and outcomes. Unfortunately the full
analysis of the study has not been completed but the data
does show that cannabis provides benefits in terms of fewer
hospitalizations and better quality of life. One interesting
preliminary finding is that cannabis seems to additive in terms
of the number of drugs that a patient uses. Vandry has not seen
a lower use of conventional medications among the medical
cannabis users. He was, however, quick to remind the data is
preliminary.
In closing, Vandry hit on a subject that would weave in and out
of the weekend’s presentations: accurate dosing. With so many
cultivars of medical cannabis available (both in terms of the
plant chemovars and administration routes) “trying to collect
and accurately gauge the information has been a monster.”
Current cannabis-based medicines: a clinician’s
perspective
Kirsten Müller-Vahl is a neurologist and psychiatrist in
Germany where she works at the Hanover Medical School. She
advocates a “pragmatic” approach when using conventionally
available cannabis-based medicine (CBM) or synthetic
cannabinoids such as nabilone. She noted that several
CBMs are legally available in Germany including pure THC
(dronabinol) and pure CBD:THC at a 1:1 ratio (Sativex). She
says that “in most patients, very soon it becomes clear, whether
or not CBM are effective and well-tolerated” but it can take
time to adjust individual treatment. She advised doctors to
pay attention to a patient’s preferred method of administration
indeed she stressed it is “important to acknowledge patients’
preferences.”
Müller-Vahl advises the inhalation route whenever possible and
advises that sometimes a combination of routes is preferable.
And she made a plea for researching other substances, noncannabinoids,
that can also have an effect on the ECS. For
example, the tongue twisting substance “palmitoylethanolamide
(PEA) enhance(s) the action of [the endogenous cannabinoid]
anandamide through an increase in the affinity for receptors
and/or a decrease in enzymatic degradation achieving a so
called “entourage effect” and enhanc[ing the] beneficial effects
of CBMs.” In other words, there are substances out there that
can have a dramatic impact upon the ECS that we need to
study as much as externally available cannabinoids.
Epidemiological Characteristics, Safety And Efficacy
Of Medical Cannabis In Older Subjects
Ran Abuhasira, of Israel’s Tikun Olam, studied the data
of 1,946 patients who were aged 65 years or more. They
suffered from a variety of ailments including cancer, nonspecific
chronic pain, Parkinson’s disease, post-traumatic stress
disorder, inflammatory bowel disease and others. The average
age was 75.8 years. At the six month follow-up a total of 1,010
patients were evaluated. There had been some deaths (249)
and some who stopped the treatment (165). Of the remaining
596 patients, 87.7% reported symptom improvement in
their condition. Among the symptoms noted were pain, sleep
distrubances, anxiety, weakness and digestive problems.
The Effect Of Cannabis On Crohn’s Disease Patients
In yet another study conducted under the auspices of Tikun
Olam, Timna Naftali studied the effect of cannabis on
Crohn’s disease. This relatively small study (total of 39 patients
with 18 receiving cannabis and 21 a placebo) looked at Quality
of Life (QOL) scores as well as the Crohn’s disease activity
index (CDAI). Improvement in the CDAI among those
receiving cannabis was significant (dropping from 279.3 to
118.6 after eight weeks of treatment). The placebo group CDAI
also dropped but far less significantly (291.2 to 212). In the
QOL scoring there was little movement in the placebo group
(71.6 before the study, 79.9 after) whereas the cannabis group
showed dramatic improvement (74.8 to 93.6).
These findings are tantalizing for those afflicted with
inflammatory bowel disease (IBD) which includes Crohn’s
disease. In the U.S. there are 1.6 million patients with IBD.
Medical Cannabis for ADHD: A Medical Sociological
Patient Case Study of Cannabinoid Therapeutics in
Finland
Aleksi Hupli’s case study of an adult ADHD (attention
deficit/hyperactivty disorder) patient in Finland highlights
an interesting conundrum encountered by cannabis scientists
and ADHD patients alike: numerous studies have explored
cannabis and ADHD but most studies, according to Hupli,
“interpret cannabis use automatically, and often misleadingly,
as drug abuse.” Hupli maintains that cannabis is an effective
medication for ADHD and cited a recent study from Norway
in which ADHD patients who illegally used cannabis reported
they did so to treat the symptoms of their ADHD. Hupli
concluded that among the biggest obstacles to ADHD patients
in Finland who use cannabis is the attitude and knowledge of
the attending physician.
Hupli’s presentation was underscored by a poster presentation
from Eva Milz of Berlin. She attempted a study of number
ADHD patients with cannabis flower obtained via German
pharmacies after special permission was obtained. The patients
reported an improvement in symptoms but the study was
crippled by lack of support and patients having to pay high
prices for for the cannabis flower.
Mary’s Prime Time • Issue 2 • 2018
IACM 2017: A Report from
5

Cancer and Cannabis Presentations
It is widely accepted that cannabis can be a palliative adjunct
to cancer chemotherapy: less pain, appetite stimulation,
reduction of nausea and vomiting, better sleep and less
depression are just a few of the benefits that can be obtained
through the use of cannabis. Additionally there is evidence
that some cannabinoids have anti-tumor properties. At the
IACM meeting there were reports on these aspects of cannabis
use as well several case studies presented as poster sessions.
2
Lihi Bar-Lev Schleider described a study of more than
2,000 cancer patients registered in the Tikun Olam Clinic
during a two year time period. This appears to be the largest
epidemiological study to date of the palliative use of cannabis
by cancer patients. Just over half the patients (51.2%) were
diagnosed as Stage IV and the most frequent cancers were breast
(16.7%), lung (13.6%), pancreatic (8.3%) and colorectal (8.1%).
The main symptoms were
pain (76%), sleep problems
(72%), weakness (66%),
nausea (53%) and lack of
appetite (48.8%). During the
study approximately 25% of
the patients died and another
9% left the study for varying
reasons. At the six month
followup of slightly more than
800 patients remaining in the
study 95% reported moderate
or significant improvement in
their condition. Researchers
concluded that cannabis as
a palliative treatment for
cancer patients seems to be
well tolerated, effective and
safe option to help patients
cope with the malignancy
related symptoms.
Guillermo Velasco of the
Complutense University in
Madrid, Spain gave a presentation entitled “Promising Future
Directions: Cannabinoid Medicines vs. Cancer.” Spain has
been at the forefront of the fascinating research into the antitumoral
properties of cannabis. Dr. Velasco has been studying
the topic since 2001.
At the Cologne meeting, Velasco presented data on the antitumoral
properties of cannabinoids in treating glioblastoma, an
aggressive brain tumor also known as glioblastoma multiforme
(GBM). Increasingly it appears that cannabis is best used as
an additive to chemotherapy agents. In GBM, for example,
Velasco reports cannabis and temozolomide (the primary
GBM chemotherapy agent) “produce a strong anticancer
effect, which correlates with an intense activation of cytotoxic
Cancer Presentations Highlights
autophagy” (self destruction of harmful cells). But Velasco
also cautions that much is unknown about the interactions
of cannabis with other physiologic functions. A naturally
occurring growth factor (also called cytokines) called Midkine
(MK), for example, interferes with the anticancer ability of
cannabis. Thus in individuals who may have higher levels of
MK this can lead to a bad prognosis for the GBM patient.
There are dozens of these cytokines as well as other factors
that can interact with cannabis thus contributing to an almost
individualized tailoring of therapies, a direction that oncology
is heading towards as physiology becomes better understood.
Velasco is not alone in his interest in this potential use of
cannabis. In February of this year, GW Pharmaceuticals
reported “positive top-line results from an exploratory Phase 2
placebo-controlled clinical study of a proprietary combination
of tetrahydrocannabinol (THC) and cannabidiol (CBD) in 21
patients with recurrent glioblastoma multiforme, or GBM.”
The GW study is just the latest
• A large study of cancer patients in Israel confirmed
the remarkable palliative effects of cannabis for cancer
patients. 95% of cancer patients reported moderate or
significant improvement in their conditions.
• Studies are showing cannabis in cancer treatment
is best when used as an additive to conventional
medications.
• Interaction of cannabis with other physiologic systems
is not very well understood and can make tailoring
cannabis for treatments very difficult.
• Glioblastoma seems particularly responsive to
cannabis treatment.
• Cannabis oil may be an effective therapy for patients
with malignant melanoma.
in that company’s study of the
ability of the cannabis plant
to encourage autophagy (a
natural and necessary process
of cell destruction when
something goes awry). Since
2007 GW Pharmaceuticals
has published 15 studies
on the topic. (https://www.
gwpharm.com/about-us/
news/gw-pharmaceuticalsachieves-positive-resultsphase-2-proof-concept-studyglioma)
Poster Sessions
There were also five poster
sessions that dealt with
cancer-specific topics. A
poster by Dr. Debra Kimless
underscored some of the
positive reporting in Velasco’s
session. She offered three case studies in which low dose,
whole plant cannabis was used in treating cancers. The cancers
included one case of GBM, one anaplastic astrocytoma (a rare
brain tumor) and one metastatic ALL (acute lymphoblastic
leukemia). In each case improvement was noted after use of
cannabis oil which contained both acid and decarboxylated
cannabis.
Another case study came from Frances DeForrest of Montana
and involved the use of cannabis oil to treat a malignant
melanoma. In addition to topical application of the oil the
patient also consumed one capsule daily. Oral ingestion of the
oil became a problem as the patient developed dizziness and
lethargy. Oral dosing was stopped but topical application (once
8 Cancer and Cannabis Presentations
Mary’s Prime Time • Issue 2 • 2018

a day) continued and the melanoma resolved.
Another team from Spain provided some promising pre-clinical
data on using synthetic cannabinoids to treat AML (acute
myeloid leukemia). A German team studied the effects of
CBD on the body’s “master regulators” with a goal identifying
cellular response and potential biomarkers of the antitumor
effect of cannabis. And a team from Israel looked at 13 different
chemovars of cannabis with respect to anti-cancer properties
and found considerable promise with many variations. Like the
case studies of Dr. Kimless noted above, this group determined
“whole Cannabis extracts were found to be more potent at
lower concentrations (4 μg/mL) in comparison to using pure
Δ9THC (8 μg/mL) to produce the same amount of cell death
when applied to specific cancer cell lines.”
The need for aggressive clinical study in this area is obvious.
Additionally it becomes more apparent that the whole plant is
superior to synthetics but may require significant tailoring to
individual cases until we gain a better grasp of the interaction
of the ECS with other physiological systems.
Reversal of Age-Associated Cognitive Impairments
by Ultra-Low Doses of Tetrahydrocannbinol (THC)
Such a provocative title was certain to catch the eye of
conference attendees. It is a given that we all age. And
most of us know someone who has suffered from age-related
cognitive impairment. A low dose solution of anything that
would help us adapt to these natural and often troubling
occurrences would be welcome indeed.
Presenter Yosef Sarne of the Tel Aviv University School of
Medicine has been exploring the effect of THC on the brain
since 2012. He generated significant news in May 2013 when
he announced his findings that a micro-dose of THC appeared
to protect the brain from injury. Such a finding has obvious
implications for literally dozens of possible applications from
daily supplements as a neural protectorate to treatment of brain
injury from sports, accidents, cerebral events, or war.
Presented by Yosef Sarne, Tel Aviv School of Medicine
toxicity, epileptic seizures or neuroinflammation. Injection
of THC either seven days before or seven days after the
“insult event” provided the mice with reduced inflammation
and improvement in symptoms. Remarkably these positive
outcomes were effective for up to seven weeks.
The goal of the study presented at IACM was to determine
whether the same ultra low dose of THC would reverse agedependent
cognitive decline. The aged mice (18-24 months)
were tested with a series of standard cognitive tests and fared
significantly worse than young mice (3-4 months) in the same
tests. Old mice who were injected once with low-dose THC
fared significantly better then their cohorts who were not
injected with THC. Indeed they “performed similar to naive
young mice in all the tests.”
After announcement of his findings in 2013, Sarne continued
his research and pharmaceutical startup Therapix Biosciences
has begun the formal process of moving the drug (in this case
the existing synthetic cannabinoid, dronabinol) through the
Food and Drug Administration for possible marketing in the
U.S.
Sarne’s previous study focused on mice and ultra-low doses
of THC (0.002 mg/kg) following introduction of a brain
“insult” which could be hypoxia, deep anesthesia, MDMA-
Sarne further reported that his team discovered the THC
injection elevated the amount of SIRTI1 proteins which
have been suggested to play a part in the pathology of various
neurodegenerative diseases and mediates the effects of
melatonin, caloric restriction, and resveratrol (a natural phenol
produced in response to injury). The precise import of this
discovery remains to be seen but this demonstrates, once again,
the remarkable interaction of cannabinoids on the entire
physiology of the individual, in this case mice.
Cannabis Treatment in Hospitalized Patients Using the
SYQE-EXO Inhaler: Results of a Pilot Open Label Study
Presented by Elon Eisenberg, Technion-Israel Institute of Technology
Clinicians around the world are begging for methods that
allow accurate dosing of cannabis for their patients. So
the presentation by Elon Eisenberg of Syqe (sī/kēē) was highly
anticipated and it did not disappoint. The Syqe-Exo Inhaler
can go a long way towards helping the physician establish
appropriate dosing regimens, even remotely. Beyond that,
it can allow patients to continue using inhaled cannabis in
environments that have zero tolerance for smoked or vaped
products, e.g. hospitals, nursing homes and even schools.
The Syqe-Exo is a modified version of the Syqe inhaler
which, like many inhaler products, allows the user to insert
a cartridge with pre-measured doses that can be inhaled as
directed. The technology is so clever that some versions allow
Mary’s Prime Time • Issue 2 • 2018
Reversal of Age-Associated Cognitive Impairments
9

emote controlled dosing, in other words the inhaler can be
programmed by a signal from the healthcare practitioner. This
allows regular dosing but can be over-ridden to allow as needed
doses. And if that isn’t enough for you listen to this: “The
Syqe Inhaler utilizes selective 100 microgram dosing precision,
realtime thermal & flow controllers, lung interfacing and
wireless connectivity.”
One more amazing thing: the inhaler uses raw plant material,
not oils, allowing the patients to benefit from all aspects of
the raw plant.
The study reported in Cologne involved the re-designed Syqe-
Exo, specifically engineered for environments that must avoid
the “personal and environmental hazards of smoking.” This
was an open label study, meaning there was no attempt to
disguise the drug to either the patient or the hospital staff. The
study is ongoing and Eisenberg reported on 22 participants
thus far. All used either smoked or vaporized cannabis legally
before their admission to the hospital and the study. The device
gained high marks for ease of use, perception of inhalation end,
and overall satisfaction with the device.
What is particularly appealing about the device is the efficiency
of delivery. In the reported study “patients consumed
significantly reduced amount of daily Cannabis in comparison
to their current home use: 54 mg [32-96] mg vs 1000 mg [660-
3300] mg per day.”
Barring unforeseen events, it seems fair to predict that Syqe
inhalers have a bright future in cannabis therapeutics. For
further information: http://www.syqemedical.com.
And Syqe is not the only one looking at inhalation of cannabis
powder via inhalers. A Poster session by Andreas Boeckl
of Flurry Powders in California. He reported successful
production of inhalant ready cannabis dry powders. http://
flurrypowders.com
Cannabis Chemovars and Genetics
Report prepared by Justin Kander
Research & Development Coordinator, Aunt Zelda’s
Cannabis is a particularly unique plant in the botanical
world, and there has been continuous disagreement
about how to describe it. Two talks in Cologne addressed the
increased understanding of the plant’s history and chemical
nature and is leading to a revolution in its classification.
Ultimately this will help everyone work better with the plant.
Dr. Ethan Russo, a foremost authority of cannabis botany and
chemistry, shared important facts about cannabis classification
and chemistry in his talk "Chemovars (and a Comparison of
sativa and indica).”
The cannabis species was first formally described by Carl
Linnaeus, the Swedish botanist who pioneered the binomial
naming system of organisms. In his seminal 1753 book Species
Plantarum, Linnaeus classified the cannabis plant as one
species – Cannabis sativa. The French biologist Jean-Baptiste
Lamarck later described another form of the plant, Cannabis
indica; however, there is no current scientific consensus on
whether cannabis is one species or several. There may be several
species or one species with several subspecies. Thankfully, the
taxonomy of cannabis is not crucially relevant to its medical
use, which is determined by measurable biochemistry.
From the medical perspective, what really matters about
cannabis is the cannabinoid and terpenoid profile. The
combination of these chemicals influences medical potential.
THC and CBD are the most prominent cannabinoids, and
their ratio essentially controls the psychoactive potential of a
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Mary’s Prime Time • Issue 2 • 2018

given plant. Dr. Russo discussed a new system for classifying
cannabis developed by Dr. Ernest Small in Canada: Type
I (high-THC), Type II (mixed THC/CBD), and Type III
(CBD-dominant). Dominant terpenoids can be added to the
Type, thus quickly identifying the nature of a cannabis plant.
For example, a Type III-myrcene plant would be expected to
have no THC-like psychoactivity and be sleepy, whereas a Type
I-limonene plant would be very psychoactive and stimulating.
Dr. Russo is particularly passionate about abandoning the term
"strain" from cannabis nomenclature. That term applies to
bacteria, not plants. He believes the optimal term is chemovar,
since the chemical variety of cannabis is most important for
medical use. Focusing specifically on the chemical constituents
of any individual chemovar is the best way to predict effects,
rather than the "sativa-hybrid-indica" terminology which
dominates the industry.
Dr. Russo was recently involved in a blinded human trial that
illuminated many interesting observations about the roles
of THC, CBD, and terpenoids. Not surprisingly, patients
who used THC and CBD together had less intoxication
and sedation than patients who use THC alone. The THC/
CBD users also had reduced anxiety and increased calmness,
alertness, focus, energy, and ability to function. The presence
of myrcene appeared to decrease energy and alertness, ocimene
produced calming effects, and limonene and pinene increased
focus. The combination of limonene, ocimene, and linalool
promoted "inspiration". More research will reveal how specific
cannabinoid/terpene interactions produce unique effects in
humans.
It was encouraging to hear Dr. Russo state that advanced
genetic modification techniques or synthetic approaches are
not necessary to take full advantage of the possibilities from
cannabis. Through selective breeding, growers can create any
type of plant they want, it just takes time.
Another presentation titled “Biochemical Genomics of
Cannabis Strain Diversity” by Jonathan Page, a plant biologist,
described the biochemical pathways by which cannabinoids
and terpenes are produced. While much of the deep science
is not applicable to medical usage, it is interesting to know
how the cannabinoids are made. In fact, Dr. Page pointed out
that the cannabis plant uses "very tricky" chemistry to produce
cannabinoids, engaging in enzyme reactions never before
seen in plants. Ultimately, two important compounds known
as olivetolic acid and geranyl diphosphate combine to form
cannabigerolic acid (CBGA), the parent cannabinoid. This
is further converted to THCA, CBDA, and CBCA by their
respective synthase enzymes. The neutral cannabinoids like
THC are not directly produced by the plant and only occur
through the decarboxylation of the acidic cannabinoids.
Selective breeding affects levels of various synthase enzymes
by changing the DNA of plants across generations. The first
growers who initiated the resurgence of high-CBD plants were
really developing chemotypes with a DNA sequence that coded
for more CBDA synthase than THCA synthase.
With all the progress in genetics, it is now possible to start
finding more concrete answers about the potential differences
between hemp and medical (“drug-type”) cannabis, as well as
indica and sativa. Dr. Page collaborated with Dr. Sean Myles
of Dalhousie University to explore this, and found hemp was
indeed its own unique group and may have a different origin
than drug-type cannabis. To analyze sativa and indica, Dr. Page
had to rely on the reported ancestry from growers (% sativa/
indica) compared to the genetic ancestry he analyzed. He found
there was a moderate correlation between the two ancestries,
but overall there is not enough evidence yet to determine
whether the sativa/indica classification is truly correct.
In the future, it will be possible to predict the chemical profiles
of cannabis plants by analyzing their DNA. Interestingly, Dr.
Page worked with Dr. Tim
Hughes at the University of
Toronto in 2011 to undertake
complete genetic sequences
of three types of cannabis.
At the time, cannabis was
only the 22nd plant species
sequenced and the first ever
medicinal plant sequenced.
Such work which contributes
to our understanding of
cannabis genetics will enable
better breeding and targeting
of specific chemovars to
specific conditions.
Justin Kander
Five speakers presented information on the legal status of
cannabis in their respective countries: Canada, France,
Germany, Israel and the United States. Globally, it seems,
the status of cannabis reform is good with significant progress
in each of the countries represented. But the reports also
demonstrated the complexities that are involved in extricating
the world from more than eighty years of global prohibition.
Dr. Jeffrey Hergenrather, reporting on the U.S.A., made this
Cannabis Law & Politics
Report prepared by Alice O’Leary Randall
Editor-in-Chief, Mary’s Prime Time
point abundantly clear with his presentation. He started
with the “bright side” facts: 70% of Americans live in
states that allow medical cannabis, 90% of all Americans
support legal access to cannabis for medical purposes
while 60% support full legalization. But Hergenrather
chose to take off the rose-colored glasses and provided
some stark figures about U.S. incarceration statistics. The
U.S. currently has about 2.4 million individuals behind
Mary’s Prime Time • Issue 2 • 2018
Cannabis Law & Politics
11

ars with half that number jailed for drug offense. Despite
approximately a half dozen legislative proposals on the federal
level that would reform the general prohibition, Hergenrather
was not optimistic about passage but he did note that the U.S.
Food and Drug Administration is currently reviewing the
scheduling status of cannabidiol (CBD). It is unclear when a
decision might be forthcoming but with epidiolex (the G.W.
Pharmaceutical drug) rapidly completing its final FDA hurdles
it is likely an affirmative action will be taken so the drug can
move to market.
The story in Canada is radically different with full legalization
scheduled for July 2018. Canada’s nationwide medical cannabis
program has operated for over 15 years but the program is, in
the words of one writer, “staid” by comparison with the U.S.
state programs. There are no legally sanctioned dispensaries.
There are approximately 200,000 patients (a number that
is increasing by 5-10% every month, according to session
presenter Dr. Mark Ware) and 59 companies that service them.
Patients obtain the substance by courier or mail order. Another
7,500 patients have permission to “grow their own” plants. But
the big story is the coming legalization and what impact that
will have on medical patients. Will legalization overwhelm
the medical program? Dr. Ware expressed concerns about the
possibility. He recently served on a government committee that
has recommended leaving the medical program exactly as it is
… for the time being.
Israel is, without question, the current powerhouse of the
medical cannabis movement. Speaker Ilya Reznik rather
understatedly noted that conditions in Israel with respect to
cannabis are “very friendly.” Per capita, Reznik claims that
Israel has the largest number of medical cannabis patients in
the world. According to Reznik the Israeli Ministry of Health
is becoming more active in the issue and is moving towards
certification of pharmacies as dispensing agencies. In tandem
the agency is calling for the “medicalization” of cannabis
products which will “ensure on the one hand an appropriate
indication for patients, access to care and supply of good
quality cannabis products, and on the other hand appropriate
oversight of a product that is defined as a “dangerous drug.”
The “dangerous drug” statement is a nod to the international
treaties that bind Israel (and nearly every other nation) to
strictly uphold the provisions of the antiquated U.S. Single
Convention on Narcotic Drugs of 1961 and its sister treaty
on psychotropic drugs from the early 1970s. This drive to
“medicalization” of cannabis will undoubtedly lead to yet
another explosion of research & development from the tiny
nation in the Middle East. U.S. companies are flocking to Israel
and partnering with companies there to conduct Phase 1 & 2
studies on their products. The American companies can then
return home and pursue final Phase 3 studies for the necessary
FDA blessing. It is a strategy that seems all the more viable since
Israel recently approved the export of cannabis.
Germany enacted a law in the first quarter of 2017 that
“legalized” cannabis for medical use. According to presenter
Franco Grotenhermen “We have a fantastic law that doesn’t
work.” The regulations for the German program are still being
promulgated and Grotenhermen does not anticipate having
German-produced cannabis until 2019. In the interim the
country will need to depend on imports from the Netherlands
and Canada. The law does not limit the doctor with respect
to indications for which cannabis can be prescribed but in
order to participate in the program doctors will be subject to
“questioning.” This could have a substantial chilling effect on
physician participation. Like many speakers at the conference,
Grotenhermen bemoaned the lack of education in medical
schools with respect to the endogenous cannabinoid system
(ECS).
Sébasien Béguerie of France began his presentation by noting
that France was a leading country in herbalist practices until the
early 20th Century. Like most nations, France began the process
of “forgetting” cannabis in the early 1940s when it abolished the
French herbalist diploma and then removed cannabis from the
country’s pharmacopeia in 1951. Current patients who require
medical cannabis in France have few options. Since 2002 there
have been four cases in which patients were prosecuted for
cultivation of cannabis. All cases resulted in a guilty finding
but with no jail time or fine levied. Sativex, the cannabis-based
oral spray developed by G.W. Pharmaceuticals for treatment
of multiple sclerosis, was approved in 2013 but the French
National Authority for Health has disagreed with respect to
the distribution price and, as a result, the drug is not available
to patients. Beguerie ended his talk with a plea for education
in France that will allow physicians and law enforcement to
recognize medical cannabis patients.
Another report on country status was provided by a Poster
Session authored by Frédérique Bawin from Belgium, a
European country that has taken no steps to provide cannabis to
medical patients. Some MS patients have been able to acquire
the GW Pharmaceutical drug, Sativex. All other patients are
out of luck with respect to legal access. Ms. Bawin is a student at
Ghent University and is studying the impact of this prohibition
on the patients of Belgium.
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Mary’s Prime Time • Issue 2 • 2018