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CANNABIS CLASSIFICATION:

A MULTIDISCIPLINARY REVIEW

KNOWLEDGE, PERCEPTION AND ACCEPTANCE OF BELGIANS ON MEDICAL CANNABIS

Matthias Pav

Student number: 01407455

Promotors: Prof. dr. ir. Geert Haesaert Prof. dr. Hans De Steur

Master’s Dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of Master of Science in Bioscience Engineering Technology: Agriculture and Horticulture - main subject Horticulture

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i De auteur en de promotoren geven de toelating deze scriptie voor consultatie beschikbaar te stellen en delen van de scriptie te kopiëren voor persoonlijk gebruik. Elk ander gebruik valt onder de beperkingen van het auteursrecht, in het bijzonder met betrekking tot de

verplichting de bron uitdrukkelijk te vermelden bij het aanhalen van resultaten uit deze scriptie.

Augustus 2020

Promotoren: Tutor: Auteur:

Prof. dr. ir. Geert Haesaert Prof. dr. ir. Geert Haesaert Matthias Pav Prof. dr. Hans De Steur

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ii Acknowledgements

This master thesis addresses ‘Classifying Cannabis: a multidisciplinary review, knowledge, perception and acceptance of Belgians on medical cannabis’.

I proposed myself to present a master thesis addressing Cannabis, convinced about the increasing importance of this plant, from a social, scientific and economic point of view. Indeed, I consider this subject very interesting, completing my studies and opening the future.

Indeed, I am also deeply convinced that the use of medical cannabis urgently deserves to be studied, regulated and authorised. Medical cannabis should serve as an alternative were other synthetic drugs reach their limits.

My sister is multi-handicapped (with CHARGE syndrome, she is inter alia deaf-blind and is non- verbal) and could for sure benefit of the medical cannabis positive effects in specific moments of highest frustration and internal nervous tension.

I would like to thank Prof dr. ir. Geert Haesaert en Prof. Hans De Steur, my promotors and both high level scientists. My thanks for their support, notes and comments all through this thesis preparation. Also, my strong appreciation for all the other people I could count on, scientists and entrepreneurs, my family and friends, for their advice, help and daily support. Furthermore, I want to thank the University of Ghent and all the professors and assistants who helped me broaden my horizon, knowledge and experience during my years at the Faculty of Bioscience-engineering.

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iii Preambule Covid-19

Ik deed zelf het voorstel om een masterproef te doen rond Cannabis, omwille van het groeiende maatschappelijk, wetenschappelijk en economisch belang van deze eeuwenoude plant. Ik vond dit een mooie en relevante aanvulling op mijn opleiding.

Ik kon al snel rekenen op de steun van Prof. dr. ir. Geert Haesaert en er zou een onderzoek opgezet worden rond ‘Mogelijkheden van Cannabis voor de Vlaamse telers’. Eerst en vooral moesten echter de juridische grenzen van het project afgecheckt worden: wat kan en mag er gebeuren met Cannabisplanten voor wetenschappelijk onderzoek? Het wachten op duidelijke antwoorden zorgde al voor vertraging in de opstart van een praktische proefopstelling.

Uiteindelijk strooide Covid-19 half maart helemaal roet in het eten: een praktische proef was met onmiddellijke ingang uitgesloten…

In overleg met Prof. dr. ir. Geert Haesaert besloten we mijn masterproef te heroriënteren: - Een literatuurstudie rond de classificatie van Cannabis

- Een enquête i.v.m. de kennis en perceptie van Cannabis bij de Belgische bevolking

Voor dit tweede deel dat het praktisch werk moest vervangen, werd Prof. dr. Hans De Steur aangeduid als promotor

‘Deze preambule werd in overleg tussen de student en de promotor opgesteld en door beiden goedgekeurd.’

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iv Abstracts

Cannabis is an emblematic example of a multipurpose crop, cultivated since millennia, with enormous

social and economic value, with endless applications including food, fiber, construction materials, paper, biofuel and with numerous pharmacological properties. Cannabis has recently seen a resurgence of interest although still largely prohibited worldwide. Prohibition has resulted in an alarmingly unregulated Cannabis industry and in obstruction to scientific research, resulting in a knowledge vacuum, misconceptions and taboos. Popular non-scientifically-based terminology and claims are often confused and inconsistent with scientific evidence and formal taxonomy. The purpose of this multidisciplinary review is reconciliating popular terminology and claims with the ancient and recent scientific evidence and objectively present Cannabis’ origin, distribution and botanical, physiological and pharmacological characteristics, aiming at informatively clear up misconceptions and potential biases towards Cannabis. Additionally, an entire section is devoted to assess the Belgian public’s knowledge, perception and attitude towards medical cannabis via an online survey and statistical analysis. Six possible classificatory approaches were identified to classify

Cannabis. The chemovars method is the most powerful classification approach currently existing to

distinguish between Cannabis cultivars, offering relatively well-defined information on therapeutic and psychoactive experience, based on the terpenoid and cannabinoid combined profiles. Results indicate significant lack of knowledge, of the Belgian public, about medical cannabis, as expected, whilst participants expressed an overall positive attitude towards medical cannabis. This study recommends reassessing the lacking education on (medical) Cannabis overall but most importantly in higher education.

Cannabis is een emblematisch voorbeeld van een multifunctioneel gewas, dat al millennia wordt

verbouwd, met een enorme sociale en economische waarde, met eindeloze toepassingen zoals voedsel, vezels, bouwmaterialen, papier, biobrandstof en met tal van farmacologische eigenschappen.

Cannabis stond de laatste tijd opnieuw in de belangstelling, hoewel het wereldwijd nog steeds

grotendeels verboden is. Verbod heeft geleid tot een alarmerend ongereguleerde cannabisindustrie en tot belemmering van wetenschappelijk onderzoek, resulterend in een kennisvacuüm, misvattingen en taboes. Populaire niet-wetenschappelijk onderbouwde terminologie en beweringen worden vaak verward en zijn niet consistent met wetenschappelijk bewijs en formele taxonomie. Het doel van deze multidisciplinaire review is het verzoenen van populaire terminologie en claims met het oude en recente wetenschappelijke bewijs en objectief de oorsprong, verspreiding en botanische, fysiologische en farmacologische kenmerken van Cannabis voor te stellen, met als doel op informatieve wijze misvattingen en mogelijke vooroordelen ten opzichte van Cannabis op te klaren. Bovendien is er een hele sectie gewijd aan het beoordelen van de kennis, perceptie en houding van het Belgische publiek

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v ten opzichte van medicinale cannabis via een online enquête en statistische analyse. Er werden zes mogelijke classificerende benaderingen geïdentificeerd om Cannabis te classificeren. De chemovars-methode is de krachtigste classificatiebenadering die momenteel bestaat om onderscheid te maken tussen Cannabis cultivars, en biedt relatief goed gedefinieerde informatie over therapeutische en psychoactieve ervaring, gebaseerd op de gecombineerde profielen van terpenoïden en cannabinoïden. De resultaten wijzen op een aanzienlijk gebrek aan kennis bij het Belgische publiek over medicinale cannabis, zoals verwacht, terwijl de deelnemers over het algemeen een positieve houding tegenover medicinale cannabis hadden. Deze studie beveelt aan om het gebrek aan onderwijs over medicinale cannabis te herevalueren, vooral in het hoger onderwijs.

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vi Table of Contents

Acknowledgements ... ii

Preambule Covid-19 ... iii

Abstracts ... iv

Table of Contents ... vi

List of abbreviations ... viii

List of tables ... x

1 Introduction ... 1

2 Literature review ... 3

2.1 What is Cannabis ... 3

2.1.1 Introduction, an ancient crop ... 3

2.1.2 Geographical origin and distribution ... 5

2.1.3 Formal taxonomy ... 8

2.1.4 Drug-type Cannabis ... 13

2.1.5 Hemp versus drug-type Cannabis ... 21

2.1.6 Cannabis botanics ... 24

2.1.7 Cannabis physiology ... 26

2.1.8 Trichomes, a resin factory and classificatory tool ... 30

2.1.9 Multipurpose crop, a different perspective ... 33

2.2 The chemistry of Cannabis ... 35

2.2.1 Introduction to Cannabis secondary metabolites ... 35

2.2.2 Cannabinoids ... 36

2.2.3 Three main chemotypes ... 45

2.2.4 Terpenes, the Entourage ... 47

2.2.5 Chemovars, the future ... 50

3 Belgians’ Knowledge, Perception and Acceptance of medical cannabis ... 55

3.1 Consumer research on medical cannabis ... 55

3.2 Materials and methods ... 59

3.2.1 Participants ... 59

3.2.2 Survey design ... 60

3.2.3 Data analysis ... 62

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vii

3.3.1 Sample description ... 64

3.3.2 Belgians Knowledge, Perception and Attitude towards medical cannabis 66 3.3.3 Correlations between the Knowledge, Trust, Perception and Attitude towards medical cannabis ... 69

3.3.4 Relationships between socio-demographic characteristics and the Reason for Interest in medical cannabis ... 71

3.3.5 Relationships between socio-demographic characteristics and their Knowledge, Trust, Perception and Attitude towards medical cannabis ... 72

3.3.6 Limitations ... 76

3.4 Conclusion ... 77

4 References ... 81

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viii List of abbreviations

ATT: Attitude

BLD: Broad Leaf Drug-type BLH: Broad Leaf Hemp BP: Perceived benefits CBC: Cannabichromene CBD: Cannabidiol CBDA: Cannabinoid acid CBG: Cannabigerol CBN: Cannabinol

CFS: Chronic fatigue syndrome ECS: Endocannabinoid system GM: Genetically modified NLD: Narrow Leaf Drug-type NLH: Narrow Leaf Hemp OK: Objective knowledge RI: Reason for Interest RP: Perceived risk

SK: Subjective knowledge ST: Social trust

THC: Tetrahydrocannabinol

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ix List of figures

Figure 1: A page from a 1234 AD edition of the Pen-ts’ao with an illustration and medical description of the Cannabis plant (Cerino et al., 2020) ... 4 Figure 2: Feral Cannabis plants growing in a concrete culvert (left) and as weed in a corn (Zea mays subsp. mays) field (right) ... 6 Figure 3: The spread of cannabis, by the hand of humans, from its putative homeland in Central Asia (J. M. McPartland, 2018) ... 7 Figure 4: On the left; Harvard professor Dr. Richard Evans Schultes with Afghani BLD Cannabis plants, he identified as Cannabis indica, in harvested field in Kandahar, Afghanistan, in December 1971. In the middle; A Hemp (C. sativa) fiber field in the Netherlands, sown close together to promote stalk elongation and fiber yield, as Carl Linnaeus might have known the plant and called C. sativa (NLH). On the right Himalayan NLD Cannabis escapy from a nearby cultivation, that developed long branches and reaching a great size (Clarke & Merlin, 2013). ... 9 Figure 5: The origin of different morphologies of Cannabis, division made by simple phenotypic traits like the size of the leaves (Henry, 2018). ... 10 Figure 6: An example of a popular anti-Cannabis propaganda poster from 1936. ... 13 Figure 7: The renowned cultivator and medical cannabis user, Lambsbread, checks the tops of his 4.26 m tall “Lemon Kush” plant in Southern Oregon (Flava, 2017) ... 25 Figure 8: Cannabis sativa, scientific drawing by Franz Eugen Köhler (1887) with a

flowering male branch (left) and a fruiting female branch (right) ... 29 Figure 9: Left: a terminal branch with the whitish appearance of the pistils (stigmas) of the clustered female flowers indicating that many are receptive to being fertilized by pollen. Right: the brownish appearance of the pistils indicating that the stigmas are o ... 29 Figure 10: Three types of Cannabis trichomes are visible; capitate-stalked trichomes, capitate sessile trichomes and cystolitic trichomes (on the tip) (picture by Kenneth

Kearney) ... 31 Figure 11: excerpt from Small & Naraine, 2016b paper “Size matters: evolution of large drug-secreting resin glands in elite pharmaceutical strains of Cannabis sativa” comparing sampled fiber cultivars and drug strains by gland head morphology. ... 32 Figure 12: Multipurpose Cannabis crops throughout the Himalayan foothills of western Nepal. ... 34 Figure 13: Biosynthetic pathway of THC and CBD ... 43

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x List of tables

Table 1: Revised vernacular nomenclature graphic by J. McPartland in 2014 ... 20

Table 2: “Cannabis Terpenoid Activity Table” excerpted from “Taming THC” paper by E. B. Russo, 2011 ... 49

Table 3: Construct validation on Cronbach alpha coefficients. ... 63

Table 4: Overview of the participants socio-demographic characteristics ... 65

Table 5: Reasons for interest in medical cannabis ... 66

Table 6: Overall scores for the statements belonging to the six constructs ... 68

Table 7: Correlations between the six construct ... 71

Table 8: Relationship between the socio-demographic characteristics of the participants towards their reason for interest in medical cannabis ... 72

Table 9: Cross-tabulation of socio-demographic characteristics and Knowledge, Trust, Perception and Attitude towards medical cannabis by mean scores ... 75

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1

1 Introduction

The current climatic and economic scenario pushes toward the use of sustainable resources to reduce our dependence on petrochemicals and to minimize the impact on the environment. Plants are precious natural resources because they can supply both phytochemicals and lignocellulosic biomass.

Cannabis sativa L. is a controversial, notorious and ancient crop. It is one of the most ecologically

successful and widespread plants in the world and has been cultivated for millennia. This is due to its rich repertoire of phytochemicals (presenting an immense range of pharmacological applications), its fiber (for rope, clothing and other textiles), oil and seed (for food) and its agricultural features, namely its excellent stress resistance properties (against pests and diseases), well-developed root system preventing soil erosion and lower water requirement compared to other crops (e.g. cotton). As such this fast-growing plant is an emblematic example of a multi-purpose crop that has the potential to be an environmentally friendly alternative for limitless applications such as food products, textiles, biodegradable plastics, paper, paint, biofuel (energy), animal feed, lighting oil and most significantly as a healthier alternative or adjunct for currently marketed pharmaceuticals and clinical therapies. However, Cannabis has been prohibited in the majority of the world since the beginning of the 20th century. Due to negative propaganda campaigns and the following legal prohibitions often led by industry figures seeing Cannabis as an economical rival or to fuel racially based conflicts. One of the many consequences has been the prohibition and obstruction to scientific research efforts towards

Cannabis in its totality and its phytochemicals and this for the past century and even up to the present

day. This led to a subsequent inevitable knowledge vacuum on Cannabis that was partially filled by a pseudo-scientific (clandestine in nature) assumptions made by popular Cannabis culture, or more commonly referred to as the Cannabis community.

Cannabis has recently seen a major resurgence of interest in both the scientific community and public.

The reconciliation of vernacular and scientific knowledge has proven difficult especially in regard to

Cannabis classification. Many different parties have contributed to Cannabis’ classification and

categorization as well as many classificatory methods have been proposed and are currently (often in a flawed way) used. Furthermore, prohibition on Cannabis has seriously harmed the hemp industry as well as caused the medical and recreational Cannabis industry to be alarmingly unregulated, untransparent and lacking official standard control practices.

On one hand, an in-depth literature review aims to provide a comprehensive outlook from an objective, scientifical, multidisciplinary perspective on the scientific evidence surrounding Cannabis. On the other hand, this review also aims at reconciling the scientific-based evidence with assumptions and believes as well as non-scientifical terminology commonly used in the Cannabis community. The complicated, confusing and often vague classification of Cannabis may have been the biggest stumbling block worldwide for legislation changes in regard to Cannabis. Therefore, in the first chapter of this review, emphasis will be put on the different ways Cannabis has been classified throughout history, providing a basic understanding of Cannabis’ origin, spread and distribution in order to clear up the incredible classificatory confusion that exists today.

The second part of this review will move its focus towards “Cannabis’ chemistry” (phytocompounds) and their myriad of biological activities. This, firstly because it is key to create a comprehensive and standardized classification useful for medical practitioners, patients, recreational users and breeders alike and secondly because it might have been the single most important reason for the debate, prohibition, the confusion and the stigma that still surrounds Cannabis today.

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2 As part of this multidisciplinary review of Cannabis, the social and psychological aspect of Cannabis will be examined. More specifically, this study aims to assess the Belgian public knowledge, perceptions and how those different factors influence the attitudes towards medical cannabis as well as how differences in perceptions and attitudes relate to different “knowledge levels” and socio-demographic groups. For this purpose, 6 latent variables (Subjective and Objective Knowledge, Social Trust, Perceived Benefit, Perceived Risk and Attitude) are measured via a survey. Although similar research exists for different topics (e.g. genetically modified foods) this study is the first of its kind in regard to the Cannabis. Based on the results of this study, recommendations are made regarding necessary legislation changes in Belgium as well as for relevant future research on Cannabis.

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3

2 Literature review

2.1 What is Cannabis

2.1.1

Introduction, an ancient crop

Cannabis is a genus of flowering plants (Angiosperms) belonging to the family of the

Cannabaceae together with Humulus (hop), the nearest relative of Cannabis, and eight other genera (Ernest Small & Naraine, 2016b).

Accurately determining the phylogenetic tree and origin of Cannabis is difficult. The reason being that print fossils of this genus are exceptionally rare but more importantly Cannabis is characterized by having a great ecological flexibility (J. M. McPartland, 2018). The latter contributed to Cannabis’ successful worldwide spread together with Cannabis’ power to create psychoactive compounds which attracted humans’ attention early on. In Robert C. Clarke and Mark Merlin seminal work “Cannabis: Evolution and Ethnobotany” it is suggested that

Cannabis was one of the first plants to be intentionally cultivated by humans, and that it played

a fundamental role in the development of settled agriculture itself (Clarke & Merlin, 2013; E. B. Russo, 2007).

Although humans and Cannabis’ first encounters are naturally lost in prehistory, it is generally thought that Man had begun to utilize the plant well before the end of the Paleolithic era, around 10,000 years ago (possibly even earlier). Archeology provides many fragmentary insights into ancient uses of Cannabis as a fiber and as a mind altering substance (Clarke & Merlin, 2013). Such archeological records, that can be found in the literature in abundance, include for example; an archeological site in the Oki Islands near Japan that contained

Cannabis achenes, hemp fiber imprints found on Yangshao culture pottery and the oldest

packaged drug-type Cannabis found in history that was found in a tomb of a Chinese shaman in the Gobi Desert, dating back from around 8000 BC (indeed 10000 years ago), 5000 BC and 680 BC respectively (Long et al., 2017; E. B. Russo et al., 2008; Wayland Barber, 1992). The oldest known written record of Cannabis’ healing properties is mentioned in Chinese Emperor Nung’s pharmacopeia, The Pen Ts’au, from at around 2700 BC. It describes the

Cannabis use to treat more than 100 ailments, like female weakness, gout, rheumatism,

malaria and constipation (Mathre, 1997). The Pen Ts’au is still used by practitioners of Chinese medicine today and this is just one example of the innumerable other written records of such ancient and traditional uses of Cannabis, from diverse parts of the world, that can be found throughout the literature.

Indeed, Cannabis has been suggested, throughout history, as treatment for a wide range of conditions relating to pain, inflammation, and mental illness which should definitely be kept in

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4 mind when progressing through the chapter two of this review that addresses modern clinical research evidence on Cannabis, where many parallels can be drawn with the ancient uses. Furthermore, to treat this wide range of ailments the Cannabis plant was used in a wide variety of manners as well as different parts of the plant were used. The latter, interestingly and often overseen by modern medicine, indicates that other different types of beneficial compounds can be found more or less concentrated in different parts of the Cannabis plant as will be discusses in chapter two. To illustrate this concept, traditional Chinese medicine used the inflorescences to treat acute pain, mania, insomnia, coughing and wounds, the leaves to treat malaria, roundworm, scorpion stings and hair loss, the stem barks were used for strangury and physical injury and the Cannabis roots, which are rarely discussed in the literature, to treat strangury, spotting, vaginal discharge, difficult births, retention of the placenta and physical injury (Jin et al., 2020).

The Latin plant name and genus Cannabis comes from the Greek word κάνναβις (kánnabis) (The Oxford English Dictionary (OED), 2019) which is loaned from the Persian kanab which was in his turn derived from the Scynthian or Thracian. Both are ancient tribes of nomadic

Figure 1: A page from a 1234 AD edition of the Pen-ts’ao with an illustration and medical description of the Cannabis plant

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5 warriors that lived in large areas of southern Siberia & Eastern and Southeastern Europe respectively and are believed by some historians to have played role in the early spread of

Cannabis (E. B. Russo, 2007). The Germanic word (Proto-Germanichanapiz) that gives rise

to the English word hemp (old English hænep ) may be a very early Germanic loan from the same Scynthian or Thracian source (Kroonen, 2013). This does not come as a surprise since

Cannabis and hemp refer to one and the same plant, Cannabis sativa L, even though they are

often used arbitrarily and interchangeably in the literature and common language. Thus, from an etymological angle, the word hemp originally and still formally refers to Cannabis sativa L. (Clarke & Merlin, 2013).

The origin of the word “canvas” can also be traced back to a Scynthian or Thracian source. The word canvas is derived from the Old French chanevaz that derives from the Vulgar Latin cannapaceus which in his turn originates from the Greek κάνναβις. Both chanevaz and cannapaceus literally mean "made of hemp" (Harper, 2000). The latter is also rather unsurprising since from the sixteenth to the eighteenth century, hemp and flax (Linum

usitatissimim L.) were the major fiber crops used in Russia, Europe, and North America (van

der Werf, 1994).

Transcendent art works, as for instance Rembrandt’s, Van Gogh’s and Gainsborough’s, were principally painted on hemp canvas, as were in fact nearly all canvas paintings from that era (Drug Paraphernalia Control Act, 1986).

2.1.2

Geographical origin and distribution

Cannabis belongs to the Rosales, an order of flowering plants, and is believed to be native

from the mountainous areas of central Asia (possibly today’s Mongolia or Southern Siberia) (Clarke & Merlin, 2013; Worsfold et al., 2019). It is theorized that the semi-nomadic tribes that first discovered its uses quickly began to cultivate it as well as spread it when humans migrated to new lands, taking seeds with them as frequently throughout history (Clarke & Merlin, 2013; Hillig, 2005). Although firm evidence supporting this often is lacking, it is believed that in such way, from Central Asia, Cannabis spread in all directions over the last ten thousand years. In South and Southeast Asia it diversified into taller, shrub varieties today known as Asian C.

indica, which also enhanced the biosynthetic capacity to produce higher concentrations of

tetrahydrocannabinol (THC), a phytocompound in Cannabis which is mainly responsible for it’s psychoactive properties. It moved northwards, towards the poles, losing stature and intoxicating ability with every degree further away from the more temperate zones as well as west into Europe where it would later be known as C. sativa (Clarke & Merlin, 2013). However, these theories were till not so long mostly based on wild-type plant distribution data from biogeographers.

Determining Cannabis’ origins and history in this fashion is precarious by the fact that

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6

Cannabis easily becomes naturalized when used as agricultural crop and subsequently

survives as a ‘‘feral escape’’ in the same area (J. M. McPartland, 2018). Feral Cannabis is highly adaptable and can grow and reproduce in a wide variety of temperate and tropical habitats and even under extreme or competitive conditions such as in a concrete culvert or as formidable weed in field crops as shown in figure 2 (Clarke & Merlin, 2013).

Today, this makes finding “natural” wild relatives of Cannabis complicated to nearly impossible. Nevertheless, according to some, finding and preserving “wild type” Cannabis plants (also known as landraces) is quite worth the effort since they offer unique chemical profiles or in the words of Russo “very interesting psychopharmacological characteristics and/or effects that are not seen in modern cultivated varieties (cultivars)”. In the Cannabis community, the term “landrace” referrers to a Cannabis genotypes that has a long grown (for many generations) outdoors in a geographic area and has consequently ecologically adapted to the local environmental conditions such as climate, pests and soil type. Hence, these more ancient plants are more vigorous than the newer hybridized Cannabis plants that have largely replaced them in places such as Southern Africa, Nepal, Jamaica, Colombia, Morocco, Afghanistan and Thailand (E. Russo, 2020).

In 2018, two meta-analyses assembled the wild-type plant distribution data known before, with fossil pollen studies (FPSs) in Asia and Europe (J. M. McPartland et al., 2018, 2019). These studies identified the northeastern Tibetan Plateau as the Cannabis center of origin, which somewhat aligns with the previously accepted central Asian origin theory but suggests a prehistoric dispersal (thus predating Homo Sapiens) of Cannabis to Europe. The latter finding

Figure 2: Feral Cannabis plants growing in a concrete culvert (left) and as weed in a corn (Zea mays subsp. mays) field (right)

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7 refutes however, the widely accepted concept that Cannabis’s dispersal to Europe depended upon human transport that was mentioned earlier (J. M. McPartland et al., 2018).

Instead of the differences between C. sativa and C. indica being due to human selection, and therefore not ‘‘natural”, McPartland concludes it is likely that during a glacial maximum,

Cannabis populations were forced to seek refugia in southern Europe and southwestern East

Asia, possibly leading to specific traits events giving rise to European C. sativa and Asian C.

indica.

Whether or not Cannabis’ geographical spread was prehistoric or by humans, both theories seem to agree when it comes to the outcome of the such an ancient dispersal event, which is also the main conclusion of this section on the geographic origin of Cannabis. Roughly speaking, from Central Asia Cannabis has spread, leading to a genetic drift that initiated allopatric differences in morphology and more importantly chemical profile.

Generally speaking, European C. sativa became characterized by low THC levels (hence, having no psychoactive effects) in contrast with the psychoactive Asian C. indica with mind-altering abilities (J. M. McPartland et al., 2018).

Figure 3: The spread of cannabis, by the hand of humans, from its putative homeland in Central Asia (J. M. McPartland, 2018)

The exact way Cannabis spread throughout the whole world is still up to debate and mostly forever lost in the murk of history. Figure 3 depicts one example of the many different hypothesized spreading models of Cannabis.

One thing is certain, through artificial selection of desirable qualities and for a variety of purposes depending on the time and place (for example bigger, more fragrant plants, those

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8 that produce better fiber or oil, or those that are found to elicit a desirable intoxicating effect) humans have been manipulating and spreading Cannabis plants for millennia ever since farming began (Clarke & Merlin, 2013; E. B. Russo et al., 2008). Its own phenotypic plasticity, ecological flexibility coupled with our eagerness to offer an evolutionary helping hand, has given us the vast diversity of genetics, morphologies and chemical profiles that we witness today in a wide variety of geographic terrains, altitudes and latitudes (Worsfold et al., 2019).

2.1.3

Formal taxonomy

The complicated, obscure and confusing evolutionary history of Cannabis may have been the biggest stumbling block for the till recently still inconclusive taxonomic organization and classification (Sawler et al., 2015). Several botanists have contributed to clarification of the taxonomy of Cannabis in recent decades (including Small and Cronquist 1976-1979, Hillig and Mahlberg 2004-2005, Clarke and Merlin 2013, McPartland, 2018). Whilst some aspects have gained more acceptance namely because the application of modern genomic tools, some disagreements can still be found regarding circumscription (what variants should be grouped), rank (whether given variants should be called varieties, subspecies or species) and which classificatory character(s) should be applied when classifying Cannabis (Ernest Small & Naraine, 2016b). All three of these points of disagreement will be addressed in this review and special attention will be given to the classification and the general vocabular surrounding

Cannabis. Indeed, this has been extremely contentious while it is key for understanding,

exploiting and controlling the plant as well as creating the appropriate policies. No single, clear, widely accepted classificatory approach exists when it comes to Cannabis. Often the approach used serves a single and limited purpose designated for the specific situation or field it is applied for. Therefore, some proposed classification methods, taxonomy and terminology found in the literature and used by the Cannabis community will be presented and discussed later. However, some important aspects of the Cannabis plant need to be introduced first.

2.1.3.1 Linneus and Lamarck

Carl Linnaeus, who the first classified and named the species Cannabis sativa in 1753, knew

Cannabis as a fiber-type, non-intoxicant cultivated plant in Europe (Green, 2005; Lynch et al.,

2016). The word "sativa" means plant species that are cultivated (Linnaeus, 1753). In fact, by that time hemp fiber was a well-established product in Europe. It played for example an important role in maritime western colonization; hence, hemp fiber was used for various maritime purposes such as making ropes, sails, water-resistant clothing etc. For example, the sails on Christopher Columbus' (1492) ships were made from hemp (Clarke & Merlin, 2013; Rogers, 2012). Since the publication, Linnaeus’s Species Plantarum is treated as the starting point of botanical nomenclature and C. sativa has nomenclatural priority.

In 1785, European naturalist Jean-Baptiste Lamarck described and named what he considered to be a different species, Cannabis indica, that he found and thought to be native from India

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9 (hence indica) (Clarke & Merlin, 2013). Lamarck’s description of C. indica differed from his description of the European C. sativa L. - denoting use of the Linnean system of taxonomy - by ‘‘very distinct’’ morphological and chemical differences. These distinguishing characteristics include more branching, a thinner cortex, narrower leaflets and, more importantly, the general ability of C. indica to induce a state of altered consciousness when consumed (i.e. psychoactive properties) as well as producing a strong odor (Piluzza et al., 2013).

Even though Cannabis appears in different growth forms depending on where and why it grows (low nutrient vs. high nutrient environment, wild-growing vs. cultivated, habitat allowing unrestricted root formation vs. restricted space as on figure 2) - figure 4, on the right side, depicts an example of how Lamarck might have known Cannabis he named Cannabis indica Lam. (Clarke, 2016).

In the 1970’s, according to McPartland, 2018, Schultes, the man who created the original taxonomy for Cannabis, misidentified Afghani plants as C. indica plants. This claim is based on the fact that Lamarck was entirely unfamiliar with Afghani Cannabis and his protolog of C.

indica describes plants that where very different than those described by Schultes.

Nonetheless both plants have psychoactive properties which might have led to this confusion.

Figure 4: On the left; Harvard professor Dr. Richard Evans Schultes with Afghani BLD Cannabis plants, he identified as Cannabis indica, in harvested field in Kandahar, Afghanistan, in December 1971. In the middle; A Hemp (C. sativa) fiber field in the Netherlands, sown close together to promote stalk elongation and fiber yield, as Carl Linnaeus might have known the plant and called C. sativa (NLH). On the right Himalayan NLD Cannabis escapy from a nearby cultivation, that developed long branches and reaching a great size (Clarke & Merlin, 2013).

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10 2.1.3.2 Leaf size and psychoactivity

Based on simple phenotypic traits as the size of the leaves and psychoactive properties, the plant Carl Linnaeus identified as C. sativa L., a fiber-type, non-intoxicant cultivated plant in Europe, is categorized, by most taxonomists, as “European Narrow Leaf Hemp” (NLH). Following the same logic, Lamarcks’s C. indica, would be categorized as ‘Narrow Leaf Drug-type Cannabis” (NLD) and Schultes’s Afghani Cannabis plants as ‘Broad Leaf Drug-Drug-type

Cannabis’ (BLD) (“Drug-type” referring to the psychoactive properties) (Clarke & Merlin, 2016;

Grevenstein et al., 2015). A fourth gene pool of Cannabis can be distinguished on figure 5, showing the other hemp variant, besides the European NLH, namely “Broad Leaf Hemp” (BLH), also referred to as the “Chinese Hemp“ (Henry, 2018). According to Philippe Henry,

Cannabis seeds commonly added to the popular bird feeds, marketed in Europe, originate

from this BLH Cannabis (Philippe Henry, personal communication, 2020).

According to (Clarke & Merlin, 2013) the two drug-type gene pools are morphologically distinct: “The NLD gene pool is characterized by tall stature, flexible stems with long internodes, lax, uncrowded inflorescences with a higher bract to leaf ratio, medium to large, finely serrated green leaflets, and light brown and often striped seeds.” “The BLD gene pool is characterized by plants of short stature, brittle stems with short internodes, crowded leafy inflorescences, wide coarsely serrated, dark green leaflets, and shiny” (Clarke & Merlin, 2013).

However, it is important to note that modern Cannabis varieties are mostly hybrids of all four of this major gene pools. More specifically, modern Hemp varieties (“non-psychoactive”) are probably hybrids of the two hemp gene pools (NLH and BLH) whereas modern day drug-type

Cannabis would refer to a large hybrid gene pool of NLD and BLD (Henry, 2018). Considering

this hybridization as well as the lack of objective measurable traits, this classification method, based on identifying a Cannabis variety as belonging to one of these categories, finds little to no use in today’s Cannabis industry.

Figure 5: The origin of different morphologies of Cannabis, division made by simple phenotypic traits like the size of the

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11 In the 18th to 20th centuries, botanists and taxonomists including Vavilov (1943), Schultes (1974), Small (1976) and de Meijer (1992) applied C. sativa and C. indica (as well as coining new taxa) according to their cultural biases and in some cases not in line with Linnaeus’s and Lamarcks’s original protologs (J. M. McPartland, 2018). This gave rise to decades of taxonomic confusion and skewed the perception of Cannabis biodiversity and distribution (J. M. McPartland & Guy, 2017).

However, in the literature, two taxonomic tendencies exist regarding the taxonomic rank and separate C. sativa and C. indica.

According to some authors and botanist, the Cannabis genus includes two different species,

Cannabis sativa L. and C. indica Lam. (Clarke & Merlin, 2013; Hillig, 2004). Some botanists

even proposed that the genus consists of three species, the third being C. ruderalis Janischevsky (Hillig, 2005; Janischevsky, 1924; J. M. McPartland, 2018). An alternative viewpoint is taken by others, namely that Cannabis is considered monotypic and the observable sub-populations represent subspecies (subsp. sativa and subsp. indica (Lam.) E. Small & Cronq.) of the one and only one Cannabis species C. sativa L. with four varieties (E. De Meijer, 2014).

This monotypic model was erected by (Ernest Small & Cronquist, 1976) in the first scientific study that dealt with a taxonomic distinction between hemp and drug-type Cannabis in 1976. Small et al.s taxonomic concept is relatively simple as it recommends C. sativa L. to be recognized as a single species, within which there is a narcotic subspecies (drug-type

Cannabis) and a non-narcotic subspecies (hemp), both having one domesticated and one

ruderal variety (Ernest Small, 2015). In other words, there is a two-step hierarchic classification system where the first step recognizes two subspecies based on THC content in dried female flowering tops (with 0.3% THC as the dividing point) and the second step recognizes two varieties within each subspecies, based on their domestication phase (Ernest Small, 2015; Ernest Small & Cronquist, 1976):

• Hemp

o C. sativa L. subsp. sativa var. sativa (low THC (THC<0,3%) & domestication traits)

o C. sativa L. subsp. sativa var. spontanea Vavilov (low THC<0,3%) & wild-type traits

• Drug-type Cannabis

o C. sativa L. subsp. indica Lam. var. indica (high THC (THC>0,3%) & domestication traits)

o C. sativa L. subsp. indica Lam. var. kafiristanica Vavilov (high THC>0,3%) & wild-type traits

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12 To date, there seems to be still no widely accepted consensus of whether Cannabis is monotypic or composed of two or more species. Cannabis’ ranking issue, as seen in the taxonomic classification of many other plant species (prof. Geert Haesaert, personal communication, 2020), largely depends on the definition given the term “plant species”, which is debatable by itself. If the definition of a plant species, biologically speaking, regards interbreeding and the creation of viable offspring, Cannabis is most definitely a single species, since interbreeding (as well as creating viable offspring) between all Cannabis populations is possible (Philippe Henry, personal communication, 2020).

It is however now widely accepted that Cannabis is monotypic and consists only of a single species Cannabis sativa L. (A. Hazekamp & Fischedick, 2012). Furthermore, a study using “DNA barcodes” concluded C. sativa and C. indica should not be considered different species (J. M. McPartland, 2018).

It is to be pointed out that the EU, possibly out of ease or to fit political biases, unless to maintain a common and harmonized approach, fails to recognize Cannabis sativa L. as being a single species. Indeed, it still adheres to the old two species model as found in the latest document covering the “Cannabis legislation in Europe” from the “European Monitoring Centre

for Drug addiction” where the definition of Cannabis by the United Nations in 1961 is still

applied (EMCDDA, 2018): “Since 1961, international law has defined the Cannabis plant as

‘any plant of the genus Cannabis’, to cover the species Cannabis indica and Cannabis sativa and any variety discovered in the future (United Nations, 1961).” Possibly, the idea of Hemp

(C. sativa L. subsp. sativa) and drug-type Cannabis (C. sativa L. subsp. indica) being two different species of plants, rather than the same species, aligns better with the political ideologies that the drug-type Cannabis prohibition supports.

In summary, the classification of Cannabis populations is confounded by many cultural factors, and tracing the history of a plant that has seen wide geographic dispersal and artificial selection by humans over millennia has proven difficult (Sawler et al., 2015). However, the most recent genetic research concludes we are in fact talking about one single species with multiple gene pools, non-psychoactive hemp hybrids of NLH and BLH and psycho active drug-type Cannabis hybrids of NLD and BLD (Henry, 2016; J. M. McPartland, 2018).

In this review, as is the case in the majority of the literature, Cannabis is thus a genus name (enveloping all types), referring to the plant species Cannabis sativa L. and all of its industrial, medicinal and recreational varieties, while Cannabis is a generic term for Cannabis, its drug preparations (recreational, therapeutic and medical), and sometimes also drugs that have similar effects or are based on Cannabis’ specific phytochemicals (Ernest Small & Naraine, 2016b). For instance, the latter will be used frequently in chapter three, when talking about

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13

2.1.4

Drug-type Cannabis

To complicate classification even more, the taxonomic concepts modified by some botanists as for example Schultes, Hillig and Vavilov were further remodeled by underground drug-type

Cannabis breeders in the 1980s and 1990s (J. M. McPartland & Guy, 2017).

These underground drug-type Cannabis breeders – also referred to as the “Cannabis community”, as will be discussed later - have played an important role, during the decades of

Cannabis prohibition, that impacted Cannabis research and in fact all of the Cannabis industry

till today.

2.1.4.1 Prohibition in context

In order to give context to the complex issue, with a multitude of political, sociological and economical pillars, prohibition of Cannabis is built on, the U.S. legislation will be given in a very condensed way hereafter.

In 18th and 19th century in what is today U.S., Cannabis was a popular treatment for a range of different conditions such as labor pains, asthma and rheumatism, where it was used under the form of tinctures and included in all sorts of medical preparations (Pollan, 2001).

In the beginning of the 20th century however, this all came to an end when Cannabis got dubbed “marijuana”, with a pejorative connotation, originating from the Mexican Spanish word “marihuana”, a slang term for drug-type Cannabis (Heritage, 2007; Nahler et al., 2019).

Indeed “marihuana” was a popular recreational drug in Mexico and in the 1920’s, when nearly a million Mexicans migrated into the United States, some brought with them the custom of “marijuana” smoking.

“Marijuana” smoking was also widely popular in the jazz world, which was mostly an African American dominated culture. Louis Armstrong for example felt marijuana enhanced his ability to improvise (Pollan, 2001).

Anti-Mexican and Anti-Black sentiment had begun to steep and the term “marijuana” arose as a negative correlation of its use by - as perceived by some, (including the first chief of the Federal Bureau of Narcotics in the 1930s, Harry J. Anslinger) - unsavory types like poor Mexican immigrants, blacks, jazz enthusiasts and bohemians of loose morals (Difonzo & Stern, 2014; Pollan, 2001).

Angslinger wanted legislation to pass to make the plant illegal for all uses, calling Cannabis a “foreign invader” to the United States. Negative propaganda pieces surrounding

Figure 6: An example of a popular anti-Cannabis propaganda poster from 1936.

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14 Cannabis, as for example “Reefer Madness” (figure 6) and “Mexican locoweed”, began to make headlines, effectively changing the public opinion.

Despite having countless uses and great economic and social importance within America for hundreds of years, the Marijuana Tax Act of 1937 imposed heavy, unrealistic taxes on the possession, sale and transportation of both hemp and drug-type Cannabis in the US. The federal government had effectively banned “marijuana”, paving the way for the next 80 years of Cannabis prohibition. The rest of the world soon followed or had already installed prohibition around the same time (Difonzo & Stern, 2014; Paoli et al., 2018).

Prohibition of Cannabis is a complicated and multi factorial issue, exceeding the purposes of this review. However, the bio active compounds in Cannabis were only discovered three decades after the prohibition started and their effects on the body another two decades later. The research on the latter is up to this day only in its infancy. However, the literature is clear on the Cannabis potential pharmacological power and safety profile.

This raises a key question of the underlying major motivations for the prohibition of Cannabis in the beginning of the 20th century. Was it scientific proof of harm or rather the economic gain of some industries (for ex. paper, timber, petrochemical industry, cotton and today’s big pharma) combined with political and social agenda’s mainly fueled by xenophobia?

To date, the prohibition, although relaxed or alleviated mostly regarding Hemp remains pertinent across most of the world. Despite the overwhelming evidence to the contrary (see later), “marijuana” is in the U.S. still classified in the Controlled Substances Act, established in 1970, as a Schedule I drug “with no medical benefits” (Gabay, 2013) an Cannabis is similarly scheduled by the UN as a substance which “all use are prohibited” with “very limited medical

purposes” (Abuhasira et al., 2018).

In short, since the prohibition of Cannabis was introduced in the early 20th century to counteract its widespread use as a recreational drug, the authorities worldwide banned the cultivation of any variety of Cannabis without making any distinction based on THC content (psycho-activity). This had a multitude of serious consequences, of which three will be addressed here below.

Firstly, this exhaustive ban of Cannabis unfairly harmed the hemp industry (Cerino et al., 2020). Indeed, for example, seventy to ninety percent of all rope, twine and cordage was made in the U.S from hemp until 1937. Consequently, this hemp as a fiber source was replaced mostly by petrochemical fibers (with production controlled mainly by DuPont, at that time one of the world's largest chemical companies) (Drug Paraphernalia Control Act, 1986).

Secondly, the whole Cannabis industry - whilst being an ancient crop with thousands years of history of use worldwide, it is only in the last hundred year it has been prohibited - knows a momentous resurgence over the past decade (Andre et al., 2016).

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15 Indeed, already in 1938, the Popular Mechanics magazine defined hemp as ‘‘the new billion-dollar crop’’ with about 30,000 different products derived from the fiber and the stalk of the plant. This undeniable economic potential and social value of Cannabis has been recognized during the past few years by most Western countries.

In regards to Cannabis consumption, due to the widespread self-administration (often without any medical supervision) and wide availability as a supplement, the market for retail sales of Hemp-derived CBD products had a worth of $170 million in 2016 in the United States alone and a projected market worth of hemp-derived CBD of $22 billion in 2022 (Cerino et al., 2020). Although no official figures exist for the market of “illegal” Cannabis use, Cannabis has been the most widely used illicit drug worldwide throughout many years and several preparations of drug-type Cannabis including marijuana, hashish, charas, dagga and bhang, are estimated to be consumed by 200–300 million people around the world, representing roughly one to 25 people globally (Borille et al., 2017; Gonçalves et al., 2019).

Despite Cannabis’ indisputable relevance and presence in today’s society, as will be highlighted by a survey conducted and discussed in chapter three, Cannabis and more specifically Cannabis cultivation is still illegal in most of the world. Consequently, the Cannabis industry is alarmingly unregulated.

The European Cannabis seed market also appears to be unregulated. Seeds advertised as being of the CBD chemotype have become legally available and regulated in last few years. It is not uncommon, however, that once acquired and planted they prove to be, in fact, of the THC chemotype (thus, falling under the “illegal” drug-type Cannabis jurisdiction) (Chandra et al., 2017).

The Dutch Cannabis regulation model is another good example of the problematic situation

Cannabis prohibition has induced around the world. In the Netherlands, whilst having a

substantial legal Cannabis market, it is still illegal to cultivate Cannabis. This creates a situation where coffee shop owners have to source the Cannabis illegally to run their business, known as “the back door problem” (Klein & Stothard, 2018).

Essentially, as can be seen in other countries, the Netherlands have a legal (or semi-regulated)

Cannabis market, fueled by criminally organized Cannabis cultivation. Consequently, Dutch Cannabis contains frequently, mostly low, concentrations of one or more different pesticides

as demonstrated by research conducted by the Dutch National Institute for Public Health and

Environment. In 11 out of 25 samples obtained from Dutch coffee shops they found amounts

higher than prescribed by the Herbal Medicines Directive even containing traces of illegal pesticides (Venhuis & van Der Nobelen, 2015). Although, these amounts were considered by some to be too low to be harmful when consumed, little is actually known about the amount of pesticides and the harmful effects they can have when entering the body via smoke (and therefore heated) (Niesink, 2008).

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16 Despite being legal in most of the world, or at least tolerated as is the case in Belgium, the CBD market is also unregulated and lacking standard testing practices regarding cannabinoid quantification (Janatová et al., 2018). Multiple studies in both the U.S. and Europe, evaluated CBD products for quality and content with regards to cannabinoids (the psychoactive chemicals of Cannabis), terpenes and oxidation products. They have found significant inaccurate labelling including, CBD content amounts being incorrectly labeled, inclusion of significant THC levels even though labelled with zero THC and the inclusion of ethanol without this being noted on the product label (Bonn-Miller et al., 2017; Wheeler et al., 2020).

All studies above on both recreational and therapeutic Cannabis products as well as the obvious relevance of Cannabis in our society highlight public health concerns that justifies the need for strict, appropriate and standardized regulations and standard testing practices rather than obstinate prohibition (Pavlovic et al., 2018).

The third major consequence of the prohibition is the obstruction to scientific research efforts on the Cannabis plant in its totality, its phytochemicals and their bioactivity for the past century and up to now.

Governments decades long restriction to access to Cannabis supplies for the scientific community, created a consequential and obvious “knowledge vacuum” regarding all aspects imaginable in Cannabis research (Difonzo & Stern, 2014).

“Lack of conclusive research” is indeed a common theme in Cannabis’s literature, for example regarding Cannabis’s early origins, classification, industrial potential, genome and especially regarding the bio activity of the plants’ secondary metabolites. The latter is still poorly understood, especially in comparison with the knowledge we would have had today if there would be no obstruction of research (Cerino et al., 2020; Nahler et al., 2019; Sawler et al., 2015).

It is precisely this “lack of conclusive research” politicians and authorities often use to support and justify the prohibition. An example of this can be found in Maggie De Block’s (Belgium’s minister of social Affairs and Health at the time of this study) position regarding Cannabis oil. She does not want to legalize Cannabis oil unless firm evidence shows it has no harmful effects and that it is effective for everyone (De Block, 2018). Such persistent attitude creates a “chicken and egg” problem that will not get resolved unless legalization progresses or at least, changes to legalization are introduced allowing for the cultivation of Cannabis for scientific purposes, as is seen in other parts of the world, as for example in Australia (Gates et al., 2017). This headlock on Cannabis research also impacted the present thesis research - as the well-established and internationally recognized Ghent University in 2020 - was not granted the clearance for physical research that was initially intended on the plant Cannabis sativa L. and this in spite of months of negotiations.

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17 Fortunately, some important and groundbreaking research has nevertheless been carried out over the past decades in certain parts of the world (e.g. in Israel (Raphael Mechoulam et al., 1992), U.S. (Clarke & Merlin, 2013; Devane et al., 1988; Ernest Small & Cronquist, 1976) and Canada) often, not surprisingly, on demand and strict supervision of government authorities (for example, on demand of the Police services, at the Faculty of Bio Engineering in Ghent (Vanhove et al., 2011, 2017)). Furthermore, it is appreciated that due to the recent resurgence of interest in Cannabis, because of its multi-purpose applications including high levels of phytochemicals and a rich source of both cellulosic and woody fibers, the research has equally seen a resurgence. Most relevant for this review and bringing us to the main important subject mentioned earlier, an undeniably influential, economically prosperous and worldwide underground “Cannabis community” is very alive today.

This self-titled “Cannabis community”, often referenced to as such in the literature (J. M. McPartland, 2018; Nahler et al., 2019; Sawler et al., 2015), consists of both large-scale and small-scale (home) illicit Cannabis breeders, Cannabis enthusiasts, aficionados and recreational and medical users. The small-scale or amateur home growers constitute a significant segment of the total Cannabis market, both in a quantitative and in a qualitative perspective (as pointed out by Decorte, (2010).

As of the beginning of the prohibition, in the early 20th century, this community received, in a sense, free rein in Cannabis growing, breeding and development for the next decades. This leads to the creation of pseudo-scientific inaccurately and/or poorly reported hybridizations, breeding and cultivation strategies, confused know-how and taxonomy and a Cannabis-specific vernacular (J. M. McPartland, 2018; Sawler et al., 2015). It makes studying Cannabis from a purely academic standpoint challenging as it is hard to study popular Cannabis literature and arrive to single clear conclusions, not to mention trying to reconcile colloquial, popular claims with the formal (academic) research findings.

2.1.4.2 The Cannabis community

As the complicated but nevertheless noteworthy passed century of Cannabis has been contextualized, focus can be drawn back to the classification of Cannabis sativa L. with a special attention to the drug-type Cannabis. Indeed, C. sativa subs. indica (drug-type

Cannabis) and not C. sativa subs sativa (hemp) is mainly relevant in the context of prohibition

and for the Cannabis community.

Reiterating the beginning of this section, the modified taxonomic concepts by some botanists as for example Schultes, Hillig and Vavilov were further remodeled by the underground drug-type Cannabis community in the 1980s and 1990s (J. M. McPartland & Guy, 2017) when the breeders as well as recreational and medical cannabis users started using the terms ‘‘sativa’’ (or “sativa” dominant) and ‘‘indica’’ (or “Indica” dominant) to classify drug-type Cannabis.

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18 These popular, vernacular terms are inspired by the botanical sativa L. and indica Lam. taxon’s. However, it is important to note, that they do not align or are “quite inconsistent” with these formal taxon’s - based on the protologs of Linnaeus and Lamarck - introduced first in the 18th century (J. M. McPartland, 2018; Ernest Small, 2007).

The reason they do not align, is straight forward as “sativa” and “Indica” are popularly used to classify drug-type Cannabis, while Linnaeus, gave the name C. sativa to the Cannabis variant he knew as non-intoxicant cultivated fiber-type hemp in Europe.

Presently (and in line with Linnaeus’s original protolog), C. sativa subsp. sativa should only and strictly be applied to non-intoxicant plants (Ernest Small, 2007).

Indica/sativa and “Indica”/”sativa” were used interchangeably in otherwise excellent scientific

studies conflating formal and vernacular taxonomy and creating even more confusion. Moreover, these popular names are now widespread in the Cannabis community and have, in fact, replaced the botanical nomenclature of sativa and indica, arguably, to the point of no return (J. M. McPartland, 2018).

In this review however, “sativa’’ and ‘‘indica’’ written in quotation marks refer to the vernacular drug-type classifications popularly used and sativa and indica written in italics refer to the original and formal (academic) taxon’s.

Although the taxonomic separation of the putative taxa C. sativa and C. indica remains controversial, the distinction between vernacular taxons “Sativa” and “Indica” type Cannabis plants is widespread in the marijuana community. Indeed, thousands of websites generalize about their morphological, physiological, phytochemical, organoleptic and therapeutic properties and differences (J. M. McPartland & Guy, 2017) that will be addressed below.

Morphologically, “Indica” dominant plants are considered smaller in height with broader leaves (in line with the BLD phenotype) while “sativa” dominant types are taller with long, thin-fingered leaves (A. Hazekamp & Fischedick, 2012; Sawler et al., 2015) (in line with the NLD phenotype as well as Linnaeus’s protolog of non-psychoactive NLH that he called C. sativa, which might have instigated the confusion as well).

Regarding the physiology, “Indica” plants typically mature faster than “sativa” types under similar conditions (A. Hazekamp & Fischedick, 2012). The two types tend to have a different smell, supposedly reflecting their different chemical profiles and more specifically their different profile of terpenoids which interestingly indeed fairly recently was proven to have a scientific base to some degree as will be discussed in section 2.2.5. This illustrates the efficacy of the pseudo-scientific work carried out by the underground breeders and Cannabis community in general.

In regard to organoleptic properties, “sativa”-type plants are widely believed to produce drug-type Cannabis with a stimulating, cerebral and energizing drug-type of psychoactive effect while

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19 “Indica”- type plants are reported to produce drug-type Cannabis that is sedative and relaxing (J. M. McPartland, 2018).

Lastly, and partly related to the latter characteristic, the clinical properties: ‘‘sativa’’ is recommended for treating depression, headaches, nausea and loss of appetite while ‘indica’’ is recommended for treating insomnia, pain, inflammation, muscle spasms, epilepsy and glaucoma (J. M. McPartland, 2018).

It should be stressed that drug-type Cannabis cultivars or genotypes are in the common language of the Cannabis community wrongfully named strains. The term “strain” is pertinent to bacteria and viruses, not plants, but has been internationally adopted in the Cannabis community and even to a certain extent by the scientific Cannabis community as well as in the scientific literature. For this reason, the terms cultivar and strain will also be used interchangeably during this review when contextually relevant.

2.1.4.3 Ruderalis

Besides the terms sativa and indica, a third and additional taxon commonly encountered, both in a scientific and vernacular context, is Ruderalis, derived from the word “ruderal,” indicating a plant species that is first to colonize disturbed lands, either caused naturally (e.g. wildfires or avalanches) or as a consequence of human activity (e.g. road construction, mining or agriculture). The putative species C. ruderalis (proposed by Hillig, 2005) may represent feral populations of the other types of Cannabis or those adapted to northern regions (Sawler et al., 2015). Indeed, the photos of ruderalis show plants with strong apical dominance (i.e. not branching a lot) and little branching, short in stature (table 1 right), which is consistent with a spontaneous escape of cultivated hemp (Henry, 2018; J. M. McPartland, 2018). Although no clear consensus on the origin and specific traits of this alleged species could be found in the literature, most experts agree that ruderalis should be applied as sub-specific designation for plants of Narrow Leaf European Hemp ancestor (especially Northern Europe) that escaped from cultivation (i.e. “wild-type plants”) and acquired different characteristics (Henry, 2016; J. M. McPartland, 2018; Sawler et al., 2015).

In today’s vernacular taxonomy, “ruderalis” is applied to plants that exhibit one to three characteristics: the CBD content level is almost equal to the THC content level, a wild-type morphology and/or having an early flowering physiology. Cannabis plants having the third characteristic are commonly called “autoflowering” meaning that they are day-neutral. In other words, the flowering process is not induced by light cycle (J. M. McPartland, 2018).

Today “autoflowering” drug-type Cannabis plants are considered to have acquired their early flowering trait from introgression with ruderalis type Cannabis plants. The less favorable traits that were also inherently introgressed in these modern day “autoflowering” drug-type hybrids are for instance a higher CBD content, relatively less production of the valuable resin which is

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20 typical for Hemp and dilution of the quality of the inflorescence (“bushy” flowering as opposed to a more dense, compact inflorescence) (Philippe Henry, personal communication, 2020).

Information on the origin of pure breed “ruderalis” is scares to non-existent in the literature. However, one relevant example of a cultivar having “ruderalis” ancestry is Finola. Finola is the first hemp cultivar developed for the production of hemp oil, i.e. seed, instead of fiber (J. Callaway, 2013) and in 2016 it became the most popular cultivar grown in Canada (Cherney & Small, 2016). This cultivar is a cross of two northern Russian landraces obtained from the Vavilov Institute of Plant Industry. The developers of the cultivar thought the parent stock may have been ruderalis (J. C. Callaway & Laakkonen, 1996).

In conclusion of this section on drug-type Cannabis two important points will be made.

Firstly, a reconciling of the vernacular and formal nomenclatures was proposed by John McPartland in 2014 and summarizes some of the prior discussed taxonomy (table 1): ‘‘Sativa’’ is really indica (since the term “sativa” should only be applied to non-intoxicant hemp plants), ‘‘Indica’’ is actually afghanica (C. afghanica plants were incorrectly identified as C. indica by

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21 botanist R. Schultes) and ‘‘Ruderalis’’ is usually sativa (escapee) (J. M. McPartland, 2018; O’S News Service, 2015).

A Genome-wide analyses revealed clustering in Cannabis cultivars that support the proposal above as well as it revealed and enforced the genetic separation of these 3 Cannabis types in distinct genetic clusters in a way that also reflects the ancient domestication trilogy of the genus

Cannabis (Henry, 2016).

Secondly, extensive cross-breeding between the Cannabis gene pools in the past 40 years has largely obliterated population differences to a point where categorizing Cannabis as either “Sativa”, “Indica” or “Ruderalis” has become nearly impossible (Ernest Small, 2017). Especially, between the two kinds of fiber forms and between the two kinds of drug-types forms, ubiquitous hybridization has rendered their distinctions almost meaningless (Ernest Small, 2017).

For this reason, thousands of Cannabis web shops often generalize about the origin of their strains being a certain percentage of “Sativa” and “Indica” instead of claiming it is a pure breed whilst they also generalize about its morphological, phytochemical, organoleptic and clinical properties (J. M. McPartland & Guy, 2017). Currently, these claims are predominantly based on pseudo-scientific morphological and organoleptic (smell and the type of “high”) characteristic assessments together with a lot of guesswork. For example, the Dutch Cannabis web shop giant Zamnesia claims that the “OG Kush” strain has a genetic profile corresponding to 75% “Indica” and 25% “Sativa” (as a result of mixing the cultivars “Chemdawg”, “Lemon Thai” and “Pakistani Kush”), being “highly potent, thanks to a 20% THC content” and being “effective in reducing stress and insomnia”.

It is important to keep in mind that there is no single, unbiased, widely accepted and undebated classification determinant which can be used to classify Cannabis. All determinants proposed in the literature are, some more than others, arbitrary (human-made) and thus not natural. A classificatory determinant, as for instance genetic profile or phytochemical profile, might be perceived as firm and undeniable. It is however always fixed by human hand and therefore flawed to a certain degree and influenced by personal biases. The tendency to classify in order to understand and control is a human trait, although strictly categorizing is more than often a lost cause, especially in regard to the natural world as is the case for Cannabis. A more fluent, continuous and borderless approach of division should be accepted in these cases, an idea that might have been illustrated in figure 5. It depicts the distribution of the Cannabis gene pools by the means of watercolors that are flowing over into one another.

2.1.5

Hemp versus drug-type Cannabis

This section presents the most recognized, used and politically relevant categorization that is applied for Cannabis. However, this type of categorization could arguably be considered as broadly overgeneralizing and having limited relevance for scientific research.

Afbeelding

Figure 1: A page from a 1234 AD edition  of the Pen-ts’ao with an illustration and  medical description of the Cannabis plant
Figure 2: Feral Cannabis plants growing in a concrete culvert (left) and  as weed in a corn (Zea mays subsp
Figure 3: The spread of cannabis, by the hand of humans, from its putative homeland in  Central Asia (J
Figure  4:  On  the  left;  Harvard  professor  Dr.  Richard  Evans  Schultes  with  Afghani  BLD  Cannabis plants, he identified as Cannabis indica, in harvested field in Kandahar, Afghanistan,  in December 1971
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The extraction of the fetal electrocardiogram from mul- tilead potential recordings on the mother’s skin has been tackled by a combined use of second-order and higher-order

Ondanks deze acties geniet het coffeeshopbeleid volgens een coffeeshop- houdster niet echt prioriteit bij de gemeente: “De horeca die cannabis onder de toonbank verkoopt wordt werd

Even though the Botswana educational system does not reveal serious pro= b1ems in terms of planning it is nevertheless important that officials of the Ministry

Het vierogenprincipe wordt het meest uitgevoerd, gevolgd door het begeleiden van de seksuele ontwikkeling van kinderen, het zorgen voor een open aanspreekcultuur en goed signaleren