WHAT AND WHERE IS HEAVEN?

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VISIONS AND HALLUCINATIONS

This book, which covers Visions and hallucinations, explains what causes them and summarises how many hallucinations have been caused by each event or activity. It also provides specific help with questions people have asked us, such as ‘Is my medication giving me hallucinations?’.

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also on all local Amazon sites, just change .com for the local version (.co.uk, .jp, .nl, .de, .fr etc.)


Medicines

Mitragyna speciose - Kratom

Category: Medicines - plant based

Type

Voluntary

Introduction and description

 

Kratom must be one of the most ambivalent plants on this site.  The correct botanical name for the plant is Mitragyna speciose and it is a plant indigenous to Thailand and Southeast Asia.

It has both therapeutic and abuse potential.  To see what happens when it is abused follow this LINK.

Kratom is an opioid, but it is not a conventional opioid.  Its leaves produce very complex stimulant and opioid-like analgesic effects. M. speciosa is also now being used as a means of gradually weaning people off opiates.  This gradual withdrawal, occasionally combined with ibogaine treatment at a point deemed safe, has been seen to be very effective at helping those with a very serious opiate addiction problem.

Equally important is that it is an anti-viral, an antiparasitic and an anti-bacterial, properties entirely overlooked in practically all descriptions of the plant - so not only does it relieve pain, it helps to fight the pathogen causing the pain in the first place - and this is a definition of a true healing plant.

The plant is abused because of the opioid content, but those who abuse kratom are committing a sin of monumental proportions considering its medicinal value.  By abusing it they have succeeded in convincing the authorities that it is a dangerous plant. 

the tragedy caused by stupid 'recreational' abusers

Kratom is currently illegal in Thailand, Myanmar (formerly Burma), Malaysia and Australia, although at the time of writing there was a lot of discussion in other countries as to what to do. They are even cutting down kratom trees in Malaysia and Thailand, in an attempt to stop people from using it.  Apart from the ecological disaster this is causing, it will limit supply and remove from the healer perhaps one of the most important plants in that area for healing - one researcher has even found it has anti-HIV activity.

The plant

Mitragyna speciosa is a large tree in the Rubiaceae family native to Southeast Asia. The name Kratom refers to the leaf harvested from the tree.

Mitragyna speciosa  is in the same family as coffee and is botanically related to plants like Corynanthe and Cinchona [from which we get quinine].  The trees grow to a height of about 3-4 metres tall in their native habitat, and  under the right conditions can reach up to 12-16 meters tall or more.  The leaves of the kratom tree are a dark green colour and can grow to over 7 inches long and 4 inches  wide.  Kratom is an evergreen but the leaves are constantly being shed and being replaced. 

Opiate activity

Kratom’s actions on the opioid receptors are via delta and mu receptors.  It is a very effective pain killer when taken orally.  It is principally a mu and delta agonist and has very little [if any] kappa activity.  Kratom helps to dull the 5 senses and suppress nervous sensations, but it doesn’t still the reasoning functions or the chattering mind.  If one was seeking spiritual experience of a kind other than healing, say inspiration, one would need to combine it with cannabis for example – this would then remove pain, heal and still the chattering mind.

The lack of kappa activity is key and why, to many users, it appears to be a more pleasant drug than any man made opioid pharmaceutical such as codeine or morphine or hydrocodone.  Kappa has some really rather unpleasant effects.  Opium has a small amount of kappa activity and this is one of its drawbacks, but kratom hasn’t.

But, Kratom has added complexity as we shall see, and must not be treated as a direct opium or opiate substitute, because its constituents appear to act on other receptors, giving it some interesting effects.

Location timing and storage

Alkaloid content varies from place to place and at different times, much as it does with many of the plants.  Climate, soil, time of the year, environment and so on all play their part and there may also be different geographical variants within the species. The alkaloid content of the leaves of Mitragyna speciosa is round about  0.5% to 1.5% in dried leaf. An average leaf weighs about 1.7 grams fresh or 0.43 grams dried. All this is very approximate, however.

Not only the amount of alkaloid content can change but the alkaloids themselves.  Kratom generally contains mitragynine but beyond this the alkaloids can vary quite a bit.  The alkaloid content can also vary depending on whether oxidation has taken place when the leaf has been dried, thus a dried leaf may contain different alkaloids to the fresh leaf. 

There is thus a very urgent need for some enterprising pharmaceutical company to step in here and help with the production of leaves of a predictable quality and with methods of processing - freezing for example, that preserve all the constituents and can be better distributed.  The whole leaf must be used.  We will see why shortly.

Chemical constituents and properties

We have combined the analysis from Dr Duke's plant database and a whole host of very useful papers to produce the following list of chemicals and properties.  This may be out-of-date in due course but we wanted to show the incredible value medicinally of this plant and thus took a great deal of time to pull all the research together:

Over 25 alkaloids have been isolated from kratom so far, the following list is in alphabetic order, some of these may not be present or only present in trace amounts.  Where the activity is known I have described it; antiviral, anti-bacterial and anti-parasitic activity has been highlighted:

  •  
    3-Dehydromitragynine LEAF  36 ppm – activity not known as yet
  • Ajmalicine – LEAF  usually only traces.  The alkaloid ajmalicine (also called raubasine), which is also found in Indian snakeroot (Rauvolfia serpentina) and Madagascar periwinkle (Catharanthus roseus), has multiple pharmacological activities. It is a blood thinner  [platelet aggregation]. It is a Cerebrocirculant - it increases oxygen availability in the brain, which has led to its use in cognitive disorders in the elderly and in stroke ischemia. It has sedative and anticonvulsive properties due to agonist activity at the [3H] flunitrazepam benzodiazepine receptor. It also acts as an antiadrenergic by blocking alpha-1-adrenergic receptors, which makes ajmalicine lower blood pressure and act as a diuretic by relaxing smooth muscle.
  • Akuammigine – LEAF  if it is present at all – and sources seem to disagree on this, it is only present in small amounts. It is a potent μ-opioid agonist, although not particularly selective
  • Corynanthedine – LEAF or corynantheidine, or  Corynanthine, or corynantheidine  also known as rauhimbine, is an alkaloid found in the Rauwolfia and Pausinystalia (formerly known as Corynanthe) genera of plants. Corynanthine acts as an α1-adrenergic and α2-adrenergic receptor antagonist with approximately 10-fold selectivity for the former site over the latter.  Corynanthine has also been shown to possess some activity at serotonin receptors
  • Corynantheidaline -  found in very young leaves
  • Corynantheidalinic acid  - found in very young leaves
  •  
    Corynoxeine  -  LEAF protects against “glutamate-induced neuronal death in cerebellar granule cells by inhibition of Ca2+”.  So crudely put it is a calcium channel inhibitor  Corynoxeine is also and I quote directly here “a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty”.
  • Corynoxine  - LEAF Corynoxine A and corynoxine B reduce locomotor activity in mice, which appears to be due to mediating activity in the dopaminergic system.
  • Epicatechin  - or  (-)-epicatechin. LEAF This chemical is also found in green tea, cranberry juice and dark chocolate, and has a wide array of beneficial activities. It “reduces free radicals in the blood and is a powerful antioxidant. It helps treat urinary tract infections by impairing bacteria's ability to stick to the cell walls of the urinary tract. Epicatechin mimics insulin and inhibits alpha-amylase, preventing the digestion of starch into absorbable glucose. It keeps blood sugar levels lower by inhibiting intestinal glucose absorption. Epicatechin is also able to inhibit growth of pathogenic bacteria such as E. coli and staph and it has anti-viral properties”.   Thus we have some key activity here – antibacterial, anti-viral, antidiabetic, and antioxidant.  Now from Dr Duke the rest of the activity:  Antiaggregant; Antianaphylactic; Antibacterial; Antidiabetic; AntiEBV , Antihepatitic V&D ; AntiHIV; Antihyperglycemic; Antiinflammatory; Antileukemic; Antilipoperoxidant; Antimutagenic; Antioxidant; Antiperoxidant ; Antiviral; Cancer-Preventive; Cardiotonic; Choline-Sparing; Hepatotropic; Hypocholesterolemic; Hypoglycemic ; Insulinogenic; Interleukin-1-alpha-Inhibitor; Interleukin-6-mRNA-Inhibitor; Lipoxygenase-Inhibitor; NO-Inhibitor ; Pancreatogenic ; Peroxynitrite-Scavenger; Pesticide; Propecic ; TNF-alpha-Inhibitor ; Xanthine-Oxidase-Inhibitor
  • Isomitraphylline LEAF - enhances the activity of phagocytes. Phagocytes are a type of cell within the body capable of engulfing and absorbing bacteria and other small cells and particles. So it is antibacterial. The presence of this alkaloid seems disputed.  It is found in Mitragyna parvifolia.  Isomitraphylline has shown cytotoxic activity against some strains of cancerous cells (HL-60 and U-937 leukemia).
  • Isopteropodine -  LEAF an Uncaria alkaloid possibly present in kratom, [analyses seem to differ here] has antimicrobial effects.
  • Mitragynalinic acid  - found in very young leaves
  •  
    Mitragynine – LEAF Mitragynine is usually the most abundant alkaloid, but its content can vary enormously.  For example, in one sample of Thai kratom it made up 66% of the total alkaloid, while it made up only 12% of the alkaloids from a Malay sample. Mitragynine acts on the mu- and delta-opiate receptors as an agonist. Mitragynine acts primarily via μ-opioid receptors.  It has negligible kappa activity.
    Although chemical companies have explored the use of mitragynine on its own as a pain reliever, this research has usually been abandoned simply because the side effects are unacceptable.  Thus it is this very complex combination of alkaloids that is key to both kratoms effects and its ‘safety’ .  As meeting notes from a study in Australia note:
    "It has been speculated that …. the different pharmacological profiles of pure mitragynine and the unprocessed leaf, [is because] the latter contains several other alkaloids that may modify the effects of the pure drug." . 
    Dr Duke says Analgesic; Anesthetic ; CNS-Stimulant ; Hypotensive ; Myorelaxant ; Vasodilator
  • Mitragynine-pseudoindoxyl – LEAF is the oxidation product of mitragynine and is often the major component of kratom that has been aged or stored for extended periods.  It acts as a fairly selective δ-opioid agonist with little affinity for μ or κ receptors.
  • Mitragynaline - found in very young leaves
  • Mitraphylline -  LEAF is a  non-narcotic constituent of Kratom, it also occurs in larger amounts in the bark of Uncaria tomentosa   - Cat’s Claw.   Its action on receptors appears to be unknown at the moment, but research work is based on its anti-cancer properties “ its in-vivo efficacy to induce apoptosis in human breast cancer, sarcoma as well as lymphoblastic leukaemia cell lines”.   
    According to Dr Duke it is Anaesthetic ; Antihypertensive; Antileukemic; Cardiodepressant; CNS-Depressant; Hypotensive; Immunostimulant; Myocontractant; Myorelaxant ; Vasodilator; and Protisticide  - this is exceptionally important, as it is means it is antiparasitic [Kills any member of the kingdom protista, a single-celled endo-organism ]
  • Paynanthine/Paynantheine – LEAF an abundant alkaline in Kratom, sometimes the second most abundant,  it can be as much as 9 to10% of the alkaloid content.  Also known as 9-methoxycorynantheine.  One of the frustrating aspects is that very little about it seem to have been put in the public domain.  Most medical papers simply state it “acts as smooth muscle relaxer”.  It has no activity on the mu receptor. 
  •  
    Quinine related compounds LEAF - In one study various compounds related to quinine [so not quinine itself] were also isolated  - quinovic acid 3-O-beta-D-quinovopyranoside, quinovic acid 3-O-beta-D-glucopyranoside etc.  Quinine is the flavor component of tonic water and bitter lemon.  It is a natural alkaloid having fever-reducing, antimalarial, analgesic (painkilling), and anti-inflammatory properties and a bitter taste. It is found in the bark of the cinchona tree, which as explained in the section on quinine is a relative of mitrygina speciosa.  Quinidine is the stereoisomer of quinine and is a pharmaceutical agent that acts as a heart antiarrhythmic agent.  Quinidine can lead to increased blood levels of opioids.  So although this is pure speculation these compounds may have an important role here in pain relief.
  • Rhynchophylline LEAF -  lowers blood pressure by blocking the voltage-dependent calcium and potassium channels, dilating peripheral blood vessels, and lowering heart rate. It also has antiarrhythmic properties, and prevents blood clots by inhibiting platelet aggregation and thrombosis. It also has anti-inflammatory and anti-pyretic properties.  
    According to Dr Duke it is also an Anaesthetic ; Antidementia ; Antiexcitotoxic ; Antihypertensive; Antiischemic; Antioxidant ; Antipyretic; Antiradicular [pain reliever]; Antithrombotic; Calcium-Antagonist; Calcium-Blocker ; Cardiodepressant ; Dopaminergic ; Febrifuge; Hypotensive; Myocontractant ; Neuroparalytic; Protisticide ; Sedative ; Serotonergic [antidepressant like] ; Uterotonic ; Vasodilator
  •  
    Speciociliatine (unique to kratom) LEAF  -  It is a minor constituent of this plant, and is the C3 stereoisomer of mitragynine.  The potency of this compound to opioid receptors was 13-fold lower than that of mitragynine.  This compound ‘inhibited the twitch contraction in mice in a naloxone-insensitive manner’. Naloxone is a μ-opioid receptor competitive antagonist. 
    Dr Duke says it is an Analgesic ; Antitussive
  • Speciofoline  - LEAF no more known
  • Speciogynine – LEAF frequently the third most abundant alkaloid.  Speciogynine  is not a mu agonist.  It is a corynantheidine type alkloid, but again there is frustratingly little information in the public domain
  • Specionoxeine and Isospecionoxeine – LEAF no more known
  • Speciophylline – LEAF Speciophylline (also known as uncarine-D) has shown “cytotoxic activity against leukemic cells like isomitraphylline, slightly less effectively against HL-60 and more effective against U-937”.
  • Stipulatine/Rotundifoline – LEAF Rotundifoline is another Uncaria alkaloid found in kratom, but its activities, if any, are not yet clearly understood
  • Tetrahydroalstonine  - LEAF Another indole which kratom shares with Madagascar periwinkle, which has been shown to lower blood sugar levels and acts as a blocker at the alpha-2-adrenergic receptors.
  • 7-hydroxymitragynine  - LEAF this alkaloid provides a major contribution to the effects  of the kratom plant.  It is present in the plant in much smaller quantities than mitragynine, but is a much more potent μ-opioid agonist. "The potency, calculated using pD (2) values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively. Antagonism of naloxone on concentration-response curves for 7-hydroxymitragynine confirmed its opioid effect. These results suggest that the opioid effect of M. speciosa is mostly based on the activity of 7-hydroxymitragynine."
     
    7-hydroxymitragynine, interacts with all three major opioid sites, delta, kappa, and mu, but bound preferentially to mu receptors with pKi values of 8.01 ±0.03. The relative affinities of 7-hydroxymitragynine for delta, kappa and mu receptors were 5.6% and 4.6%, and 89.8% respectively. Most research that has been done on kratom has focused on mitragynine or the whole plant, and since it has only recently been discovered that 7-hydroxymitragynine is the primary drug, there is still relatively little information on its activity and what differences it may have from mitragynine
    Those who have tested 7OHM on its own to determine its effect describe a “warm rushing calming kind of sensation, a long pleasurable (euphoric, but not to the level of full opiate agonists) come up, followed by a longer term of sedation and analgesia”  It also appears to have aphrodisiac effects, which seem to indicate adrenoceptor activity that has not yet been isolated by scientists.   It “does not seem to be as physically draining or addictive as opiates can be”.  It was also described as a hugely effective pain suppressant. “After taking just the first dose, the pain was notably reduced. After another dose the pain was gone completely. When taking the doses more rapidly the analgesic effects were some of the strongest I have ever experienced, I felt completely disconnected from my sense of touch”.
  • 9-hydroxycorynantheidine - also binds selectively to mu receptors. It is believed to be a partial agonist at mu receptors.

I think that you can see that what we have here is a highly complex and extraordinarily valuable plant, whose potential has only just begun to be explored.  Those who classify it as a simple opium or opioid substitute are overlooking the many additional properties it possesses.  There are some substances in kratom whose properties are extremely poorly understood [if PubChem and PubMed are representative] and which are chemicals that are proportionally a large part of the overall chemical content of the plant.  Two substances – Paynantheine  and Speciogynine  - which are in some samples the second and third most abundant substance seem almost unresearched [or openly researched].

 

Method

Mixing kratom with over the counter medicines as well as prescription drugs has caused deaths.  You should NOT take Kratom with alcohol. 

Do not use with  lidocaine, Beta blockers, anti-depressants or peripherally acting drugs such as loperamide, as it will intensify the  respiratory depression if the drugs are co-administered and act like an overdose.  Note that, virtually all of the negative reports involving kratom involve either large doses, multi-drug combinations, or addictive use.

There are two types of kratom which are distinguishable by the colour of the veins in the leaf - red or green (sometimes called white). The green-veined variety is supposed to have a stronger effect. Red and white veining occurs at different times in plants which were all cloned from the same mother plant – in effect the veins are an indicator of strength and strength varies over time.

 

Fresh leaf

Users in Asia use the fresh leaves of kratom and chew them. Some villagers even use the leaves in cooking.   Since some of the substances in kratom oxidise after being picked and dried, the chemical effects of dried leaf and fresh leaf are different.  Fresh leaves appear to provide more health giving and stimulant properties.  Young leaves have different chemicals to older leaves, so again the effects can differ.

When preparing fresh leaf, the vein is extracted and sometimes salt is added to try and prevent constipation. Leaves are also mixed with dried coconut, ginger, onions, nutmeg and lime and rolled with daun kaduk (wild pepper leaf) to make them a bit more palatable.  Consumption of the leaf is usually followed by drinking something hot, such as warm water or coffee.  

 

Tea

Dried leaves.  5 grams will make a tea with noticeable effects, and 15 grams will produce the strongest effects which could be dangerous. Remember that the potency differs between plants.  Given that the best effects are experienced at only fairly low doses it is better to go for well under the 15 grams.  There are suppliers who advertise stronger strains labelled as "super" or "premium" kratom.  These are expensive and pointless, given that the lower doses produce the best effects.

Most people make the tea by steeping the leaves in boiling water until the tea has cooled down and had some time to steep.  It is then strained and drunk.

In Malaysia, kratom is sold at roadside booths in the form of a tea called air ketum ("kratom water").  The Malay version of kratom tea is made by boiling leaves in water for two hours. This is then  cooled by placing the boiling pot into a bucket of cold water, enabling the drink to be sold as a cold drink in a hot land.

Side-effects

 

There are some very key medicinal properties that emerge when you examine the experiences of actual users of this plant.  Some effects of a normal mu opioid receptor pharmaceutical usually regarded as annoying or even dangerous have not been reported for doses which are low to moderate – notably respiratory depression and itching [caused by histamine release on discovering a pathogen or toxin]. 

There is a possibility that there is more adrenoceptor activity than has been identified, for example, and that it acts on the smooth muscles of the lungs to counteract the respiratory depression of the opioids. 

Hypothermia is also a side effect of some pharmaceutically based opioids, however, this too has not been reported.  One has to consider that hypothermia/cooling might be viewed in the areas in which Kratom is used to be an advantage not a disadvantage, so it has not been reported.

Predicted effect given alkaloid

Observed effect

Sedation, relaxation

 

Sedated; feel lazy relaxed; tranquilised perhaps, but not fully sedated

?

 - mild caffeine type stimulant at doses under 10 grams

 - low doses of 1.5-2 grams produce stimulation

 - it motivated the mind and body for work and study

 - is well suited to engaging in productive and creative work, exercise, or for social situations

 - I am particularly fond of going on long nature hikes after a cup of kratom tea

pleasure – via dopamine release and adrenergic action

 - waves of pleasure running through my limbs,  particularly in my extremities [!]

euphoria– via dopamine release

 

 - It is very euphoric, and makes my body feel wonderful

 - the euphoria was beyond powerful

General pain relief [analgesia] – suppression of pain from wherever it is sited

 

 - It seems to reduce pain by a lot

 - I have used it for back pain, and it worked better than any reasonable dose of a pharmaceutical Opiate/Opioid I've used

 

Empathy, feelings of love

I get some empathy and heart opening happiness

 

Spiritual experience effects

The trees seemed to sway a bit, and my sense of vision was enhanced. Colours seemed brighter. I just lay in the autumn leaves in the middle of a beautiful hollow in the woods. I felt a strong connection with nature. I felt unity and admiration of God's creation.

Mild nausea

some mild, nausea at the higher doses

controls the smooth muscle contraction of the bladder, so may have diuretic action

 

Increased urination at higher doses

constipation

Kratom has been used in South-East Asia for conditions such as diarrhea

Reduction in physical activity

‘Locomotor sensitisation opposition’

Anti-anxiety

 - Gave me a profound sense of well being

 - Stopped being anxious

Constriction of the pupil

 - Some odd feelings from my eyes, blurry vision

 - my vision was extremely distorted

References and further reading

  • Angela Merkel planting kratom trees
    "Efficacy of almitrine-raubasine in cognitive disorders of aging: a double-blind, placebo-controlled, clinical and psychometric study": Carbonin PU, Greco A, Pisanti P, Gemma A, Cattelin F [Clin Neuropharmacol. 1990;13 ]
  • "Benzodiazepine agonist-type activity of raubasine, a rauwolfia serpentina alkaloid": Charveron M, Assie MB, Stenger A, Briley M. [Eur J Pharmacol. 1984 Nov 13]
  •   Inhibition of the alpha 1 and alpha 2-adrenoceptor-mediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine - Roquebert J, Demichel P : Eur J Pharmacol. 1984 Oct 30;
  •  Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A.  León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ - Department of Medicinal Chemistry & National Center for Natural Products Research, School of Pharmacy, University of Mississippi,  USA.
  • Lydon, J. & Duke, S., The potential of pesticides from plants, pp. 1-41 in Craker, L. & Simon, J., eds, Herbs, Spices & Medicinal Plants: Recent Advances in Botany, Horticulture, & Pharmacology,  1989.
  • Collins, D.J., Culvenor, C.C.J., Lamberton, J.A., Loder, J.W. and Price, J.R., Plants for Medicines, CSIRO, East Melbourne, Australia, 1990.
  • Singleton, V.L. 1981. Naturally Occurring Food Toxicants: Phenolic Substances of Plant Origin Common in Foods. Advances in Food Research 27:
  • Uchida, U., Ohta, H., Niwa, M., Mori, A., Nonaka, G-i., Nishioka, I., and Zaki, M. 1989. Prolongation of Life Span of Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) Ingesting Persimmon Tannin. Chem. Pharm. Bull. 38(4): 1990.
  • Duke, James A. 1992. Handbook of phytochemical constituents of GRAS herbs and other economic plants. Boca Raton, FL. CRC Press.
  • Duke, James A. 1992. Handbook of biologically active phytochemicals and their activities. Boca Raton, FL. CRC Press.
  • Economic & Medicinal Plant Research, 6:.
  • Neuwinger, H. D. 1996. African Ethnobotany - Poisons and Drugs. Chapman & Hall, New York.
  • Hansel, R., Keller, K., Rimpler, H., and Schneider, G. eds. 1992. Hager's Handbuch der Pharmazeutischen Praxis, Drogen (A-D), Springer-Verlag, Berlin.
  • Iwu, M.M. 1993. Handbook of African Medicinal Plants. CRC Press, Boca Raton, FL
  • Jeffery B. Harborne and H. Baxter, eds. 1983. Phytochemical Dictionary. A Handbook of Bioactive Compounds from Plants. Taylor & Frost, London
  • Phenolic Compounds in Food and Their Effects on Health. Antioxidants & Cancer Prevention. Huang, M.T., Ho, C.T. and Lee, C.Y. eds. 1992. ACS Symposium Series 507.ACS, Washington
  • Vlietinck, A.J. and Dommisse, R.A. eds. 1985. Advances in Medicinal Plant Research. Wiss. Verlag. Stuttgart.
  • Wagner & Wolff, eds. 1977. New Natural Products (RS164. I56. 176)
  • ANON. 1948-1976. The Wealth of India raw materials. Publications and Information Directorate, CSIR, New Delhi. 11 volumes.

Phuket police chopping them down.................

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