Tag: CBD (page 2 of 7)

Cannabis and Malaria: New Study Reveals CBD is Effective in Preventing Deaths

This article was originally published on CannabisHealthIndex.com.

Malaria is a worldwide tropical disease that puts at risk about half the world’s population with the poorest nations being the most vulnerable. To make matters worse, malaria is growing resistant to the available drugs.

Malaria Patient, Nyangaton, Ethiopia (source)

Malaria Patient, Nyangaton, Ethiopia (source)

It is estimated that each year 350–500 million cases of malaria occur worldwide, and it is further estimated that of those between one to three million people die, most of them young children. The vast majority of malaria and malaria deaths occurs in sub-Saharan Africa followed at a distance by India and Brazil.

Orthodox medicine provides us some understanding of how the disease is transmitted. In a nutshell, when a mosquito bites a person with malaria the mosquito drinks infected blood. The malaria parasite (plasmodium falciparum) is easily transmitted to a new host when she bites again. Once inside the new host the parasites enters red blood cells and destroys them.

The bodies immune system initiates complex and strong response such as malaria’s characteristic high fevers and chills. Many of the cyclical phases the disease engenders are poorly understood. This is especially true with the most severe form of the illness, cerebral malaria (where the brain is undergoing sudden and severe changes).

Malarial Sporozoites (source)

Malarial Sporozoites (source)

Orthodox treatment is limited to pharmacological prevention and treatment protocols with supportive care as needed. To date all modern treatments may or may not be effective and no drug prevention protocol provides 100% protection. In the worst case scenarios physicians are left to merely manage the progression of the disease as best as they can.

There Have Been Some Advancements in the Fight Against Malaria, Including Rapid Diagnostic Tests (source)

There Have Been Some Advancements in the Fight Against Malaria, Including Rapid Diagnostic Tests (source)

It is interesting to note that malaria was once endemic in the US (eradicated only by 1951), in Poland by 1956, in Japan by 1961, on Taiwan by 1964, in Italy by 1970, or on Aneityum (South-Sea island belonging to Vanuatu) by 1996. Key to eradication in all these cases was not a drug but a basic care for nature and the environment such as underground plumbing, clean public water supplies, wastewater treatments, basic public health measures, and minimal environmental stewardship.

But, back to remedies. A quick look at the history of malaria treatments will point out nature’s continuous supportive role in preventing and saving lives.

Once first contact was made in the 15th Century, European invaders and missionaries quickly learned from local shamans. Initially, only one remedy emerged. The bitter tasting bark of cinchona. However, over time the parasite developed resistance.

19th century researchers took their molecular cue from the trees constituents and developed the first pharmaceutical (quinine) mirroring the plant power over the parasite but with enough of a difference to overcome resistance.

malaria-research

Few new pharmaceutical remedies have been developed since. And, over time each drug is rendered weaker and weaker as parasite resistance grows.

It wasn’t until much later (or millions of deaths later) that another gift from nature shifted the horrific toll on humanity. Enter a demure shrub, sweet wormwood (artemisia annua). The plant was studied in modern times by Tu Youyou, a Chinese scientist influenced by Traditional Chinese Medicine where the herb has been used to treat fever for Millenia.

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Nobel Prize Winner Tu Youyou (source)

She discovered the compound artemisinin that is now the basis for malaria treatment options. In 2015 she received the Nobel Peace Prize for her discovery which is credited with saving untold lives.

Still, as resistance is growing again new and safe treatments need to be urgently found. Luckily, nature provides us yet again with another potent possibility.

This time researchers from Brazil, responding to this urgent need, have discovered that Cannabidiol (CBD), the non-psychoactive compound of cannabis with known neuroprotective properties has the capacity to reduce inflammation of the brain during cerebral malaria.[1]

Professor Alline Cristina de Campos

Professor Alline Cristina de Campos of the Ribeirão Preto Medical School at the University of São Paulo

CBD was also found to prevent memory loss and anxiety commonly associated with this phase of the disease. The experiment was conducted on mice and while human trial are still to be conducted it is good to know that new, safe, and natural treatment options may be forthcoming.

Uwe Blesching is a medical journalist and regular contributor in the fields of cannabinoid science, mind-body medicine, phytopharmacology, and more. Blesching earned his PhD from the Western Institute for Social Research. Much of the information from his most recent book, The Cannabis Health Index, has been made available on Cannabis Reports as well.

[1] Campos AC, Brant F, Miranda AS, Machado FS, Teixeira AL. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria. Neuroscience. 2015 Mar 19;289:166-80. DOI: 10.1016/j.neuroscience.2014.12.051

Cannabis Study: CBD Generates Rapid Antidepressant Effects Via Advanced Cortical Signaling

New evidence revealed in a study from Spain (titled: Cannabidiol Induces Rapid-Acting Antidepressant-Like Effects and Enhances Cortical 5-HT/Glutamate Neurotransmission: Role of 5-HT1A Receptors) provides evidence that the cannabinoid CBD (cannabidiol) may be an effective treatment for depression. The study was published in Volume 103 of the Journal of Neuropharmacology (2016).

Depression affects nearly fifteen million adults across the United States. Every year, roughly $42 billion dollars are spent on prescription medicines for depression and anxiety, including brands like Prozac, Zoloft, and Wellbutrin. This new evidence indicates that CBD could be an effective alternative to these pharmaceutical approaches.

Materials and Methods Used in the Study

The study examined three month old mice (C57BL/6, 25-30mg) after undergoing either an olfactory bulbectomy, or a sham-operation. The mice that received the olfactory bulbectomy procedure are referred to throughout the study as OBX mice.

C57BL/6 Mice (source)

C57BL/6 Mice (source)

The olfactory bulbectomy has been proposed and secured as a model of depression used in clinical studies. After the operation, mice exhibit hyperactivity in enclosed arenas, nocturnal hyperactivity, memory deficits, changes in food motivation, and alterations within neurotransmitter systems of serotonin and glutamate production.

Open Field Tests Examine Agitation, Anxiety, and Hyperactivity

Open Field Tests Examine Agitation, Anxiety, and Hyperactivity

This study examined both behavioral and neurochemical tests. Behavioral tests included open field and sucrose preference tests, and the neurochemcial tests included microdialysis and autoradiography of serotonin receptor (5-HT1A) functionality.

Traditional Depression Medications and How Neurotransmitters Treat Depression

Traditional western medicine employs a variety of medications to treat depression. Different chemicals are used in antidepressant medication, each one targeting a specific neurotransmitter, or group of neurotransmitters. A particularly well known type of antidepressants are called SSRIs (selective serotonin reuptake inhibitors).

“SSRIs block the reabsorption (reuptake) of the neurotransmitter serotonin in the brain. Changing the balance of serotonin seems to help brain cells send and receive chemical messages, which in turn boosts mood.”

Mayo Clinic on SSRIs

There are many SSRIs with brand names that are regularly advertised on television and radio: Prozac, Lexapro, Zoloft, and more.

This study focuses on the cannabis compound CBD (cannabidiol) as a novel treatment for depression symptoms.  Activity of serotonin, glutamate, and the 5-HT1A  receptor are of particular interest for these researchers as they monitor the OBX and sham-operation mice. The results of the study indicate that CBD can provide both rapid and long-term antidepressant-like effects.

Graphical Findings from the CBD Study

All graphs are from the study: “Cannabidiol Induces Rapid-Acting Antidepressant-Like Effects and Enhances Cortical 5-HT/Glutamate Neurotransmission: Role of 5-HT1A Receptors,” with image credit going to  R. Linge et al. in Journal of Neuropharmacology: 103 (2016) 16-26 (DOI: 10.1016/j.neuropharm.2015.12.017).

Figure 1:


Fig. 1. Acute effects of CBD in the open field test. Acute CBD (50 mg/k; i.p.) significantly reversed both OBX-induced hyperactivity (A) and decreased central ambulation (B) 30 min post-injection and it was devoid of any behavioral effect in sham counterparts. Data represented as mean ± SEM, n 1⁄4 6e7 mice per experimental group (*p < 0.05 and ***p < 0.001 vs. SHAM VEH; #p < 0.05 and ##p < 0.01 vs. OBX VEH).

Figure 2

Figure 2. Time-course effects of CBD administration in the open field and sucrose preference tests. The effect of CBD upon the OBX-induced hyperactivity (A) and decreased central activity (B) was evidenced throughout the treatment assessed 24 h post 1, 3, 7 and 14 days of drug administration. Additionally, chronic CBD reversed OBX-induced anhedonia following 7 days of administration (C). Data represented as mean ± SEM of n 1⁄4 7e9 mice per experimental group (*p < 0.05, **p < 0.01 and ***p < 0.001 vs. SHAM VEH; ##p < 0.01 and ###p < 0.001 vs. OBX VEH).

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Figure 3. Differential effects of acute and chronic CBD upon 5-HT and glutamate levels in ventro-medial prefrontal cortex of OBX and sham mice. Acute CBD (50 mg/kg; i.p.) increased extracellular 5-HT in the vmPFCx of OBX-mice but not in sham animals (A), and increased glutamate levels in both groups (B). Following chronic administration, a challenge dose of CBD increased extracellular 5-HT in sham and OBX mice (C), whereas it induced an increase of glutamate efflux only in OBX mice (D). Chronic CBD did not produce any significant change in 5-HT absolute basal levels (E) though it did increase glutamate absolute basal levels in both sham- and OBX-treated mice (F). Data represented as mean ± SEM, n 1⁄4 5e7 animals per experimental group (**p < 0.01 vs. SHAM VEH; #p < 0.05 and ##p < 0.01 vs. OBX VEH).

Figure 4. Box and whiskers plot of 5-HT1A receptors functionality in different brain areas after chronic administration of CBD. A decreased (±)8-(OH)-DPAT stimulated [35S]GTPgS binding was measured in DRN, CA1-CA2, and AMY in OBX mice compared with sham animals. This impaired 5-HT1A receptor functionality in OBX-mice was restored after chronic administration of CBD. A higher (±)8-(OH)-DPAT stimulated [35S] GTPgS binding was detected in the mPFCx in all CBD-treated mice. Results are expressed as percentage of [35S]GTPgS binding stimulation over basal values, as mean ± minimum/maximum of n 1⁄4 6e9 mice per experimental group (*p < 0.05 and **p < 0.01 vs. SHAM VEH; #p < 0.05 and ##p < 0.01 vs. OBX VEH).

Figure 4. Box and whiskers plot of 5-HT1A receptors functionality in different brain areas after chronic administration of CBD. A decreased (±)8-(OH)-DPAT stimulated [35S]GTPgS binding was measured in DRN, CA1-CA2, and AMY in OBX mice compared with sham animals. This impaired 5-HT1A receptor functionality in OBX-mice was restored after chronic administration of CBD. A higher (±)8-(OH)-DPAT stimulated [35S] GTPgS binding was detected in the mPFCx in all CBD-treated mice. Results are expressed as percentage of [35S]GTPgS binding stimulation over basal values, as mean ± minimum/maximum of n 1⁄4 6e9 mice per experimental group (*p < 0.05 and **p < 0.01 vs. SHAM VEH; #p < 0.05 and ##p < 0.01 vs. OBX VEH).

Figure 5. Behavioral effects of acute CBD in OBX mice were prevented by 5-HT1A receptor blockade. In the open field test, WAY100635 (0.3 mg/kg; i.p) prevented both the reversal of OBX-hyperactivity (A) and the increase of central activity (B) induced by CBD (50 mg/kg). By contrast the selective CB1 receptor antagonist AM251 (0.3 mg/kg; i.p.) did not counteract any of these effects. Data represented as mean ± SEM of n 1⁄4 5e7 animals per experimental group (*p < 0.05 vs. vehicle-treated group; #p < 0.05 and ##p < 0.01 vs. CBD- treated group).

Figure 5. Behavioral effects of acute CBD in OBX mice were prevented by 5-HT1A receptor blockade. In the open field test, WAY100635 (0.3 mg/kg; i.p) prevented both the reversal of OBX-hyperactivity (A) and the increase of central activity (B) induced by CBD (50 mg/kg). By contrast the selective CB1 receptor antagonist AM251 (0.3 mg/kg; i.p.) did not counteract any of these effects. Data represented as mean ± SEM of n 1⁄4 5e7 animals per experimental group (*p < 0.05 vs. vehicle-treated group; #p < 0.05 and ##p < 0.01 vs. CBD- treated group).

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Figure 6. Neurochemical effects of acute CBD were prevented by 5-HT1A receptor blockade. In microdialysis studies, cortical 5-HT outflow induced by CBD in OBX animals was prevented by WAY100635 co-administration (A). In sham mice, the co-administration of WAY100635 and CBD resulted in increased 5-HT levels in vmPFCx (B). Increased cortical glutamate levels induced by CBD were also abolished by WAY100635 in both OBX (C) and sham mice (D). Data represented as mean ± SEM of n 1⁄4 5e7 animals per experimental group (*p < 0.05 and **p < 0.01 vs. respective vehicle-treated group; #p < 0.05 and ##p < 0.01 vs. respective CBD-treated group).

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Figure 7. Proposed neurochemical mechanism of action of CBD to induce fast antidepressant effects. In prefrontal cortex, CBD would potentiate the inhibitory function of 5-HT1A receptors upon GABA-ergic interneurons, favoring glutamate signaling in postsynaptic areas, the stimulation of pyramidal descending projections to DRN, and therefore the neuronal firing of serotonergic neurons, and the 5-HT increase in mPFCx. In DRN, CBD would increase the firing of serotonergic neurons by reducing the inhibitory effect of GABAergic interneurons, without the detrimental effect of somatodendritic 5-HT1A receptors which are desensitized in OBX mice, therefore leading to an increase in 5-HT levels in PFCx.

Results and Discussion: CBD as a Novel Treatment for Depression

As shown in the graphs above, the symptoms of depression were mitigated by CBD in mice that had undergone OBX and sham operations. CBD exhibited positive effects for both acute and chronic depression models. The conclusion section of the study explains the overall findings very succinctly:

“In all, CBD is a multi-target drug that can modulate a variety of systems implicated in mood control and therefore, result in a great value from a clinical point of view.

This work evidences that CBD could represent a novel drug for treating depressive disorders in a very fast manner, acting via the enhancement of serotonergic and glutamatergic transmission through the modulation of 5-HT1A receptors.

The fast onset of antidepressant action of CBD and the simultaneous anxiolytic effect would solve some of the main limitations of the current antidepressant therapies.

Furthermore, the broad range for therapeutic dosage and the lack of psychotomimetic effects confers a fundamental advantage for its use in clinical practice compared to other fast-acting antidepressant alternatives.

Finally, this novel strategy consisting in the dual potentiation of serotonergic and glutamatergic transmission could bring new light to the discovery of new fast and effective antidepressant therapies.”

Cannabidiol clearly has a role in neurotransmitter activity. Science is beginning to understand more about interactions between CBD and the many receptors involved in mood regulation, which will hopefully result in new medical approaches for treating symptoms of depression.

Cannabis Reports supports all cannabis studies because clinical data will help us all better understand our relationship with cannabis. Check out our science feed for future examinations of cannabis research. For the most up to date info on Cannabis Reports, follow us on Twitter, and like us on our Facebook page.

Study Examines Cannabinoid and Terpene Development Patterns for Three Cannabis Chemotypes

Our understanding of cannabinoid science improves with every single study published. Since the re-discovery of the endocannabinoid system, we have attempted to map the complex relationship between the plant, its chemical constituents, and the way these compounds interact with our bodies.

Taken from the Cannabis Health Index

Taken from the Cannabis Health Index

For decades, the facts of cannabis science have evolved as we better comprehend cannabinoid synthesis, genetic hybridization, and the formation of the cannabis plant in general.

title

A recent study published in the Journal of Natural Products examines the evolution of major cannabinoid and terpene production during a growth cycle of three different cannabis chemotypes. This study monitored three chemotypes of cannabis, each defined by the ratios at which they produce the acidic forms of the two most researched cannabinoids: THC (tetrahydrocannabinol) and CBD (cannabidiol).

Cannabinoid Terpene Study Journal of Natural Products

In this study, titled “Evolution of the Cannabinoid and Terpene Content During the Growth of Cannabis sativa Plants from Different Chemotypes,” the results indicate that patterns exist within different cannabis chemotypes, which is very valuable data for breeders, cultivators, and scientists.

Study Design for Evaluation of Cannabinoid Production

Determining the best methods for optimizing production of specific cannabinoids is difficult work. The results of this type of work will ultimately lead to more efficient production patterns.

The researchers from both Spain and Switzerland designed the study to measure cannabinoid and terpene content throughout the growth stages of three different cannabis chemotypes. The three chemotypes focused on heavily in this study were:

  • Chemotype I: High THCA/CBDA ratio (>1.0)
  • Chemotype II: Intermediate THCA/CBDA ratio (usually 0.5-2.0)
  • Chemotype III: Low THCA/CBDA ratio (<1.0)

Cannabis plants with high THCA/CBDA ratios are generally classified as drug-type plants. Cannabis plants with substantially higher amounts of CBD (chemotype III) are typical fiber-type plants. There are two other chemotypes (IV and V), both for fiber-type plants.

The study measured cannabinoid and terpene growth from the root growth phase (R.G.), through the vegetative phase (V.P.), and even goes past the flowering phase (F.P.) to examine post-flowering degradation of cannabinoid production.

cannabis groth phases, clones

The researchers analyzed clones from stable mothers that produced standardized chemotypical content. Approximately 50 clones were taken from each mother; chemotypes I and III were represented by three mothers each, and chemotype II was represented by only one mother. All of the clones were grown indoors under controlled conditions to eliminate as many variables as possible (20-28* C and 40-70% humidity).

Examination of Cannabinoid and Terpene Production Rates

The results and discussion of this study are complex, and you are encouraged to go and read through the full publication (4 pages) to see all of the supporting informational materials (57 great reference points).

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Above is the first graphic presented: a simple cannabinoid synthesis chart presented within the study. Beyond THC and CBD, the researchers examine the presence of CBGA, the precursor to THCA, CBDA, and the less-known CBCA.

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Figure 2 shows the content (mg/g) of three different cannabinoids (CBGA, CBDA, THCA) in the three different chemotypes (I, II, III) researched in this study. The graphs on the left are the cannabinoid contents of the leaves throughout the growth cycle, and the graphs on the right represent the cannabinoid content found within the flowers.

Please be advised on a publication typo: the y-axis of the CBGA graphs mistakenly reads CBDA content.

From the results shown above in Figure 2, you can see the patterns of cannabinoid production within each chemotype, and also the similar patterns of cannabinoid production between each chemotype. The concentrations of THCA and CBDA in the leaves exhibited the same evolution for every chemotype. Another similarity that was to be expected was that regardless of chemotype, a major increase of cannabinoids was evident during the initial stages of trichome development.

As for CBGA, the concentration of CBGA “remained constant in the chemotype I plants, whereas it decreased in plants from the other two chemotypes” after the flowering period had commenced. The authors of this study found this synthesis rate of THCA and CBGA in chemotype I varieties to be very interesting, and a subject that deserve future attention.

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Figure 3 displays data regarding the development patterns of monoterpenes and sesquiterpenes among the three examined chemotypes.

Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16.

Sesquiterpenes are a class of terpenes that consist of three isoprene units and have the empirical formula C15H24. Like monoterpenes, sesquiterpenes may be acyclic or contain rings, including many unique combinations.

-From Wikipedia, the free encyclopedia

Monoterpene production displayed the same evolution trends found with THCA and CBDA (Figure 2). Sesquiterpenes exhibited a different pattern of concentration throughout the growth cycle. After the flowering period, sesquiterpene production in all three chemotypes remained stable, whereas monoterpene concentration was abundant after the flowering phase.

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“As observed in Figure 4… there was a clear distinction between chemotype I plants from the rest (two clusters) and between the leaves and the flowers in each cluster (leaves in blue and flowers in red).

The chemotype II plant was closer to the chemotype III plants than the chemotype I plants, most likely because of its higher CBDA content. From the loading projection, the cannabinoids and terpenes of each class of samples were identified as those that are similar to CBDA and THCA. Thus, the higher CBGA and CBC content can be attributed to chemotype I plants.

Moreover, terpenes, such as β- eudesmol, γ-eudesmol, guaiol, α-bisabolene, α-bisabolol, or eucalyptol, were much more pronounced in chemotype III plants, whereas γ-selinene, β-selinene, α-gurjunene, γ-elemene, selina-3,7(11)diene, and β-curcumene were characteristic of the chemotype I plants. This chemotype-dependent terpene distribution was also observed in the correlation analysis of the data.

As indicated in Table 1, terpenes that were more pronounced in chemotype III plants had higher correlation coefficients with CBDA than with THCA. In contrast, the characteristic terpenes of chemotype I had high correlation coefficients with THCA and negative coefficients with CBDA.”

Taking Advantage of Cannabinoid Concentration Data

Cannabis has been sorely misrepresented in the scientific world, so the efforts required for studies such as this one should be appreciated by our industry and our community. The results of this particular study show encouraging opportunities for cultivators and breeders to further improve their cannabinoid production methods.

cannabis-grow-phase

Understanding cannabinoid production rates will allow for future projects and research to focus on better breeding techniques and methods for developing cannabis genetics that contain specific profiles of cannabinoids, terpenoids, and even flavonoids.

Every opportunity to increase our overall knowledge about cannabis science is a very positive step in improving the way we discuss this plant and its chemical components.

Cannabis Reports supports all cannabis studies because clinical data will help us all better understand our relationship with cannabis. Check out our science feed for future examinations of cannabis research. For the most up to date info on Cannabis Reports, follow us on Twitter, and like us on our Facebook page.

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