2.0.0 CMAP™ Checklist:
for Cannabis Research in Human Subjects (Appendix A)
2.1.0 Purpose of the Study
2.1.0.1 Exploratory
2.1.0.2 To prove a hypothesis
2.2.0 Sponsor
2.2.0.1 Institution
2.2.0.2 Private study
2.2.0.3 Not indicated
2.3.0 Bias
2.3.0.1 Sources of funding
2.3.0.1.1 National Institutes of Health (NIH)
2.3.0.1.2 National Institute of Drug Abuse
2.3.0.1.3 Pharmaceutical company
2.3.0.1.4 Private funding and organizations
2.3.0.1.5 Not for profit
2.3.0.1.6 Other:
2.3.0.2 Affiliations
2.3.0.2.1 academic
2.3.0.2.2 commercial
2.3.0.2.3 non-profit
2.3.0.2.4 governmental
2.3.0.3 Potential undisclosed bias based on:
2.3.0.3.1 personal public statements
2.3.0.3.2 interpretation and conclusions of published and unpublished studies
2.3.0.3.3 sources of funding
2.3.0.3.4 professional or academic affiliations
2.4.0 Institutional Review Board (IRB) approval
2.4.0.1 IRB run by the organization (academic or commercial) conducting independent research
2.4.0.2 IRB run by a company in the business of providing independent IRB services
2.5.0 Abstract
2.6.0 Protocol
2.7.0 Methodology
2.7.1 Subject Selection
2.7.1.1 Sampling technique
2.7.1.1.1 Controlled sampling
2.7.1.1.2 Subjects randomly assigned to a control or test group
2.7.1.1.3 Subjects self-selected
2.7.1.1.4 Single-blind
2.7.1.1.5 Double-blind
2.7.1.1.6 Exclusionary criteria in sampling
2.7.1.1.6.1 age
2.7.1.1.6.2 gender
2.7.1.1.6.3 ethnicity
2.7.1.1.6.4 use or history of use of
2.7.1.1.6.4.1 prescription drugs
2.7.1.1.6.4.2 over the counter drugs
2.7.1.1.6.4.3 recreational drugs
2.7.1.1.6.4.4 tobacco
2.7.1.1.6.4.5 nicotine vape (see Method of Administration, Sections 2.7.3.6.1.1 and 2.7.3.6.1.2)
2.7.1.1.6.4.6 nicotine transdermal patch
2.7.1.1.6.4.7 alcohol
2.7.1.1.6.5 other exclusionary criteria
2.7.1.1.7 Psychophysiological considerations
2.7.1.1.7.1 Set
2.7.1.1.7.1.1 mental state
2.7.1.1.7.1.2 expectation effect
2.7.1.1.7.1.3 double blind
2.7.1.1.7.2 Setting
2.7.1.1.7.2.1 physical environment
2.7.1.1.7.2.2 social environment
2.7.1.1.7.2.3 double blind
2.7.1.1.7.2.4 Examples:
2.7.1.1.7.2.4.1 informal by subject’s choice
2.7.1.1.7.2.4.2 formal by protocol
2.7.1.1.7.2.4.3 “mood” of the setting
2.7.1.1.7.2.4.4 experience (history of cannabis use)
2.7.1.1.7.2.4.5 subject’s circadian rhythm
2.7.1.1.7.2.4.6 other herbal supplements, over-the-counter and prescription drugs)
2.7.1.1.7.2.4.7 other active and “inert” ingredients in topicals, et al.
2.7.1.1.7.2.5 New cultivar effect
2.7.1.1.7.2.6 Typical rotation/use sequence of cultivar re tolerance not just to THC, but “entourage” or “integration” effect as well
2.7.2 Cannabis Selection
2.7.2.1 Plant Profile
2.7.2.1.1 Botanical identification (Cannabis Sativa L.)
2.7.2.1.1.1 Hybrids – bred into thousands of cultivars from variations grown from these 4 sub-species)
2.7.2.1.1.1.1 Sativa
2.7.2.1.1.1.2 Indica
2.7.2.1.1.1.3 Ruderalis
2.7.2.1.1.1.4 Afghanica
2.7.2.1.1.2 Cultivar name (e.g., “Super Lemon Haze”)
2.7.2.1.1.2.1 Cultivar’s genetic lineage: (e.g., Lemon Skunk x Super Silver Haze)
2.7.2.1.1.2.2 validation of cultivar
2.7.2.1.1.2.3 Characterization of effects of cultivar studied
2.7.2.1.2 Cultivation
2.7.2.1.2.1 Growth conditions
2.7.2.1.2.1.1 Grower-producer
2.7.2.1.2.1.2 Phenotype
2.7.2.1.2.1.2.1 seed
2.7.2.1.2.1.2.1.1 genetics verified
2.7.2.1.2.1.2.1.2 genetics not verified
2.7.2.1.2.1.2.2 clone
2.7.2.1.2.1.2.2.1 genetics verified
2.7.2.1.2.1.2.2.1 genetics not verified
2.7.2.1.2.1.2.3 indoor
2.7.2.1.2.1.2.3.1 type of lighting
2.7.2.1.2.1.2.3.1.1 LEDs (specific spectrum)
2.7.2.1.2.1.2.3.1.2 high pressure sodium (HPS)
2.7.2.1.2.1.2.3.1.3 metal halide (MH)
2.7.2.1.2.1.2.4 outdoor
2.7.2.1.2.1.2.4.1 sungrown
2.7.2.1.2.1.2.5 greenhouse
2.7.2.1.2.1.2.6 hydroponic
2.7.2.1.2.1.2.7 soil
2.7.2.1.2.1.2.8 nutrients
2.7.2.1.2.1.2.9 water quality
2.7.2.1.2.1.2.9.1 tap water
2.7.2.1.2.1.2.9.2 alkaline/ph balance
2.7.2.1.2.1.2.9.3 bottled
2.7.2.1.2.1.2.9.4 hard
2.7.2.1.2.1.2.9.5 soft
2.7.2.1.2.1.2.10 organic
2.7.2.1.2.1.2.11 not organic
2.7.2.1.2.1.2.11.1 pesticides used
2.7.2.1.2.1.2.12 wash-out period (flush)
2.7.2.1.2.1.3 Living Plant Testing
2.7.2.1.3 Harvest
2.7.2.1.3.1 harvest time
2.7.2.1.3.1.1 readiness of trichomes
2.7.2.1.3.1.2 days into flowering
2.7.2.1.3.1.3 time of day of actual harvest
2.7.2.1.3.2 Testing at harvest
2.7.2.1.4 Post-harvest
2.7.2.1.4.1 Fresh
2.7.2.1.4.1.1 raw
2.7.2.1.4.1.2 cooked
2.7.2.1.4.2 Trim
2.7.2.1.4.3 Drying
2.7.2.1.4.3.1 moisture content
2.7.2.1.4.4 Cure
2.7.2.1.4.4.1 testing
2.7.2.1.4.5 Storage
2.7.2.1.4.5.1 oxygen
2.7.2.1.4.5.2 light
2.7.2.1.4.5.3 heat
2.7.2.1.4.5.4 time
2.7.2.1.4.5.5 humidity
2.7.2.1.4.5.6 biological sterilty
2.7.2.2 Processing
2.7.2.2.1 Whole Plant
2.7.2.2.1.1 Flower
2.7.2.2.1.2 Trim
2.7.2.2.2 Extraction
2.7.2.2.2 Solvent
2.7.2.2.2.1 CO2
2.7.2.2.2.2 ice water
2.7.2.2.2.3 butane
2.7.2.2.2.3.1 purge
2.7.2.2.2.3.1.1 type of purge
2.7.2.2.2.3.1.2 test of purge results
2.7.2.2.3 Solution for extraction of fat soluble molecules
2.7.2.2.3.1 butter, oil, or fats
2.7.2.2.3.1.1 plant
2.7.2.2.3.1.1.1 saturated
2.7.2.2.3.1.1.2 unsaturated
2.7.2.2.3.1.2 animal
2.7.2.2.3.1.2.1 saturated
2.7.2.2.3.1.2.2 unsaturated
2.7.2.2.3.2 food grade ethanol
2.7.2.2.3.2.1 alcohol content/evaporated
2.7.2.2.3.2.2 alcohol content/not evaporated
2.7.2.2.3.3 food grade glycerin
2.7.2.2.3.3.1 glycemic load
2.7.2.2.3.4 food grade propylene glycol
2.7.2.3 Laboratory Analysis
2.7.2.3.1 Cannabinoid profile (partial) – see Glossary and Other Resources, Section 1.4.1.3.7
2.7.2.3.1.1 CBG-A (Cannabigerol-acid)
2.7.2.3.1.2 CBG (Cannabigerol)
2.7.2.3.1.3 THC-A (tetrahydrocannabinol-acid)
2.7.2.3.1.4 THC (tetrahydrocannabinol, THC, Δ9 , Delta-9- after decarboxylation)
2.7.2.3.1.5 THC 11 (tetrahydrocannabinol – 11)
2.7.2.3.1.6 THCV (Tetrahydrocannabivarin)
2.7.2.3.1.7 CBD-A (Cannabidiol)
2.7.2.3.1.8 CBD (Cannabidiol – after decarboxylation)
2.7.2.3.1.9 CBC-A (Cannabichromene-acid)
2.7.2.3.1.10 CBC (Cannabichromene – after decarboxylation)
2.7.2.3.1.11 CBN-A (Cannabinol-acid)
2.7.2.3.1.12 CBN (Cannabinol – primarily found as a result of THC breakdown during storage, not from CBN-A oxidation)
2.7.2.3.1.13 Other cannabinoids
2.7.2.3.2 Terpene profile (partial) There are more than 100 terpenes with a range of effects — many well studied in other plants; they are a major driver of the “entourage effect” and many terpenes cross the blood-brain barrier. The following list includes some of the major terpenes, other plants in which they are found, and some of their reported effects.
2.7.2.3.2.1 Monoterpenoids (highly volatile and likely to be lost or diminished during drying and early storage)
2.7.2.3.2.1.1 Borneol (camphor, rosemary, and mint) – anesthetic, anti-inflammatory, analgesic
2.7.2.3.2.1.2 Cineole (eucalyptus) – analgesic for topical uses, stimulant
2.7.2.3.2.1.3 cis-Ocimene (variety of plants and fruit) – used in perfumery
2.7.2.3.2.1.4 Limonene (orange peel) – hypothermogenic
2.7.2.3.2.1.5 Linalool (lavender) – relaxant, anesthetic, anti-convulsant, analgesic, anxiolytic, burn therapeutic agent, anti-depressant (via seratonin-receptor transmission amplification)
2.7.2.3.2.1.6 Myrcene (hops) – sedative for sleepiness, analgesic, muscle relaxant
2.7.2.3.2.1.7 a-Pinene (pine) – bronchodilator, memory retention aid, anti-bacterial, anti-inflammatory; crosses the blood-brain barrier easily.
2.7.2.3.2.1.8 Pulegone (rosemary) – may prevent short-term memory loss (acetylcholinesterase protein inhibitor)
2.7.2.3.2.1.9 Terpinolene (cumin, lilac, apple, tea-tree and conifers) – anti-septic, anti-bacterial, anti-fungal, preservative, treats insomnia in a blend of lilac and lavender.
2.7.2.3.2.1.10 Terpineol (lilac, apple blossoms) – used in perfumes, cosmetics, and flavorings.
2.7.2.3.2.1.11 Others
2.7.2.3.2.2 Sesquiterpenoids (less volatile)
2.7.2.3.2.2.1 a-Caryophyllene or Humulene (hops, pine) – anti-inflammatory
2.7.2.3.2.2.2 b-Caryophyllene (black pepper) – anti-inflammatory, analgesic, protects cells lining the digestive tract, binds to CB2 receptors
2.7.2.3.2.2.3 Caryophyllene oxide (oxidated Caryophylene) – anti-fungal, anti-bacterial
2.7.2.3.2.2.4 b-Eudesmol (Chinese herb) – anti-convulsive
2.7.2.3.2.2.5 trans-Nerolidol (ginger, jasmine, lavender, tea tree, lemon grass) – flavoring, perfumery, and may enhance skin penetration for transdermal delivery of therapeutic drugs
2.7.2.3.2.3 Other Cannabis Terpenes
2.7.2.3.3 Flavinoid profile
2.7.2.3.3.1 Flavones
2.7.2.3.3.2 Flavanols
2.7.2.3.4 Vanilloid profile
2.7.2.3.4.1 Vanilloids
2.7.2.4.5 Contaminants
2.7.2.3.6 Lab QA Program and Testing (per Washington State Liquor Control Board – WSLCB)
Washington State Liquor Control Board (to become WS Liquor and Cannabis Control Board), WAC 314-55-103 “Good Laboratory Practice Checklist.” (for certification of I-502 products), PDF, pp 7-9. http://www.liq.wa.gov/publications/Marijuana/I-502/Good_Laboratory_Practice_Certification_Checklist.pdf
2.7.2.3.6.1 Sampling/sample protocols adequate chain of custody tracking
2.7.2.3.6.1.1 sample preparation, extraction and dilution (SOP)
2.7.2.3.6.1.2 demonstration of recovery for samples in various matrices (SOP):
2.7.2.3.6.1.2.1 plant material/flower
2.7.2.3.6.1.2.2 edibles (solid and liquid meant to be consumed orally)
2.7.2.3.6.1.2.3 topicals
2.7.2.3.6.1.2.4 concentrates
2.7.2.3.6.1.2.5 tincture
2.7.2.3.6.1.2.6 spray
2.7.2.3.6.1.3 Whole plant sampling method (cannabis selection)
2.7.2.3.6.1.3.1 Location of sample
2.7.2.3.6.1.3.1.1 Specific location (bud, leaves, high, low)
2.7.2.3.6.1.3.1.1 Several locations averaged
2.7.2.3.6.1.3.2 Homogenization
2.7.2.3.6.1.3.3 Weighing
2.7.2.3.6.1.3.4 Labeling
2.7.2.3.6.1.3.5 Sample identifier (source, lot)
2.7.2.3.6.1.3.6 Date
2.7.2.3.6.1.3.7 Tracking
2.7.2.3.6.1.4.8 Condition of sample
2.7.2.3.6.1.4.8.1 macroscopic inspection
2.7.2.3.6.1.4.8.1.1 foreign matter
2.7.2.3.6.1.4.8.2 microscopic inspection
2.7.2.3.6.1.4.8.2.1 microbial contaminants
2.7.2.3.6.1.4.8.2.2 nutrients and fertilizers
2.7.2.3.6.1.4.8.2.3 pesticides
2.7.2.3.6.1.4.8.2.4 moisture analysis
2.7.2.3.6.1.4.8.2.5 residual solvent
2.7.2.3.6.1.4.8.2.6 metabolite analysis
2.7.2.3.6.1.4.8.2.6.1 beginning of testing
2.7.2.3.6.1.4.8.2.6.2 during testing
2.7.2.3.6.1.4.8.2.6.3 end of testing
2.7.2.3.6.1.4.8.2.7 sample potency
2.7.2.3.6.1.4.8.2.7.1 beginning of testing
2.7.2.3.6.1.4.8.2.7.2 during testing
2.7.2.3.6.1.4.8.2.7.3 end of testing
2.7.2.3.6.1.4.8.2.8 chemical assay procedure/method
2.7.2.3.6.1.4.8.2.8.1 method
2.7.2.3.6.1.4.8.2.8.1.1 LC
2.7.2.3.6.1.4.8.2.8.1.2 HPLC
2.7.2.3.6.1.4.8.2.8.1.3 uHPLC (aka UPLC)
2.7.2.3.6.1.4.8.2.8.1.4 GC
2.7.2.3.6.1.4.8.2.8.1.5 Headspace GC
2.7.2.3.6.1.4.8.2.8.1.6 next generation advances
2.7.2.3.6.1.4.8.2.8.2 data protocols followed
2.7.2.3.6.1.4.8.2.8.2.1 Calculations for quantification of bioactive compound content in various matrices – SOPs
2.7.2.3.6.1.4.8.2.8.2.2 Determination of the range for reporting the quantity (LOD/LOQ) data review or generation
2.7.2.3.6.1.4.8.2.8.2.3 Reporting of data: certificates of analysis (CA-clear and standardized format
2.7.2.3.6.1.4.8.2.8.2.4 Documentation that value reported in CA is within range/limits of the analytical method
2.7.2.3.6.1.4.8.2.8.2.5 Documentation that qualitative results (below LOQ but above LOD) are reported as “trace”
2.7.2.3.6.1.4.8.2.8.2.6 Documentation that method has specificity for degree of quantitation reported
2.7.2.3.6.1.4.8.2.8.2.7 Use of appropriate controls: Documentatoin of daily use of positive and neg controls that
2.7.2.3.6.1.5 Level II validation of methodology used for quantification of bioactive compounds
2.7.2.3.6.1.5.1 single lab validation parameters are demonstrated for GC, HPLC data review:*
2.7.2.3.6.1.5.1.1 linearity of reference standards
2.7.2.3.6.1.5.1.2 use of daily standard curve
2.7.2.3.6.1.5.1.3 accuracy
2.7.2.3.6.1.5.1.4 precision
2.7.2.3.6.1.5.1.5 recovery (5 determinations not less than 90%)
2.7.2.3.6.1.5.1.6 reproducibility over time within a relative standard deviation of 5%
2.7.3 Methods of Extraction (MOE); Method of Administration (MOA); Timing of Administration (TOA)
Note: Cannabis may be pre-activated (heated) or cold-extracted and activated during consumption
2.7.3.1 Heated plant – heated sufficiently to activate cannabinoids (decarboxylated)
2.7.3.1.1 examples: combust, vape, dab, edible, tincture
2.7.3.2 Partially heated plant – not heated sufficiently to activate
2.7.3.2.1 (tincture, other low temperature extracts)
2.7.3.2.1.1 Raw Plant
2.7.3.2.2 examples: juicing, fresh greens in salad
2.7.3.3 Extracts/Concentrates
solvent (if any) may be pharmaceutical grade (PH), food grade (F), Commercial ( C), Industrial (I), organic (O), plant-based (PL), or animal-based (A)
2.7.3.3.1 kief – solventless mechanical extraction
2.7.3.3.2 hash – solventless, ice water, mechanical extraction
2.7.3.3.3 hash oil – solvent extraction
2.7.3.3.3.1 butane
2.7.3.3.3.2 CO2
2.7.3.3.3.3 fats/oils
2.7.3.3.3.4 alcohol/ethanol
2.7.3.4 Ingredients in Edibles and other MOAs
Note: pharmaceutical grade (PH), food grade (F), Commercial ( C), Industrial (I), organic (O), plant-based (PL), or animal-based (A)
2.7.3.4.1 fats (butter, oil, etc.)
2.7.3.4.2 alcohol/ethanol (e.g., Everclear)
2.7.3.4.3 propylene glycol
2.7.3.4.4 glycerin
2.7.3.5 Bio-Pharma
2.7.3.5.1 Pharmaceutical extracts (e.g., Sativex)
2.7.3.5.2 Synthesized Cannabinoids (e.g., WIN-55)
2.7.3.6 Inhalation
2.7.3.6.1 Oral inhalation
2.7.3.6.1.1 Flowers (aka “bud”), hash, or other concentrates are combusted or vaporized (aka “vaped”) to decarboxylate (activate) with heat during consumption
2.7.3.6.1.2 Oils can also be pre-decarboxylated (activated) and delivered as a mist from a heated atomizer (vape pen)
2.7.3.6.2 Oral/heated and nasal/unheated combined inhalation
(e.g., Terpz inhalation system)
2.7.3.6.3 Oral or nasal inhalation of terpenes
2.7.3.6.3.1 oral
2.7.3.6.3.2 nasal
2.7.3.7 Edibles – Infused Products
(Note: may be pre-activated (A), heated before consumption; or inactive (I))
2.7.3.7.1 Raw plant
2.7.3.7.1.1 edible
2.7.3.7.1.1.1 juiced
2.7.3.7.1.1.1 salad greens
2.7.3.7.1.1.1 fresh (same day harvest)
2.7.3.7.1.1.1 storage period
2.7.3.7.2 Food and drinks
2.7.3.7.2.1 infused liquids
2.7.3.7.2.2 infused solids
2.7.3.7.3 Capsule or pill
2.7.3.8 Sublingual
2.7.3.8.1 Spray
2.7.3.8.2 Tincture
2.7.3.8.3 Candy
2.7.3.9 Topical
2.7.3.9.1 oil
2.7.3.9.2 lotion
2.7.3.9.3 cream
2.7.3.9.4 spray (e.g., for topical relief of neuropathy, arthritis)
2.7.3.10 Transdermal patch
2.7.3.11 Vaginal suppository
2.7.3.12 Rectal suppository
2.7.3.13 Intravenous injection
2.7.3.14 Timing of Administration
2.7.3.14.1 time-released capsule or caplet
2.7.3.14.2 when administered
2.7.3.14.2.1 same time each day in circadian rhythm
2.7.3.14.2.2 with meal
2.7.3.14.2.3 before meal
2.7.3.14.2.4 after meal
2.7.3.14.3 interaction with other medicines and supplements
2.7.3.14.4 interaction with types of food and drink
2.7.3.15 MOA, MOE, and TOA are matched to subject’s medical condition and purpose of study
2.7.3.15.1 Method of Administration
2.7.3.15.2 Method of Extraction
2.7.3.15.3 Timing of Administration
2.7.4 Data collection and metrics (examples):
2.7.4.1 Qualitative data
2.7.4.1.1 Self-reporting survey (with open-ended questions)
2.7.4.1.2 In-depth subject interviews
2.7.4.1.3 Field research
2.7.4.1.4 Search of relevant anecdotal literature
2.7.4.2. Quantitative data
2.7.4.2.1 Self-reporting survey (with quantitative questions)
2.7.4.2.2 Physician reporting
2.7.4.2.3 Medical records search
2.7.4.2.4 Data analysis from other studies
2.7.4.2.5 Epidemiological
2.7.4.2.6 Meta-analysis
2.7.4.2.7 Search of relevant peer-reviewed published studies
2.7.4.2.8 Serum metabolites measured
2.8.0 Data analysis
2.8.1 Qualitative Data
2.8.2 Quantitative Data
2.8.3 Statistical analysis
2.8.3. Common statistical tests and procedures (per Wiki) include:
2.8.3.1 Analysis of variance (ANOVA)
2.8.3.2 Chi-squared test
2.8.3.3 Correlation
2.8.3.4 Factor analysis
2.8.3.5 Mann–Whitney U
2.8.3.6 Mean square weighted deviation (MSWD)
2.8.3.7 Pearson product-moment correlation coefficient
2.8.3.8 Regression analysis
2.8.3.9 Spearman’s rank correlation coefficient
2.8.3.10 Student’s t-test
2.8.3.11 Time series analysis
2.9.0 Discussion
2.9.1 Discussion should reflect an understanding of the complexities of cannabis research
2.9.2 Comments:
2.10.0 Findings
2.10.1 Findings noted should be supported by the data
2.10.2 Comments:
2.11.0 Interpretation
2.11.1 Interpretation should be supported by the data
2.11.2 Comments:
2.12.0 Conclusion
2.12.1 Conclusions should be supported by the data
2.12.2 Comments:
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